Human evolutionary genetics

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Human_evolutionary_genetics 

Human evolutionary genetics studies how one human genome differs from another human genome, the evolutionary past that gave rise to the human genome, and its current effects. Differences between genomes have anthropological, medical, historical and forensic implications and applications. Genetic data can provide important insights into human evolution.

Origin of apes

Hominin timeline

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Hominini

Nakalipithecus

Ouranopithecus

Oreopithecus

Sahelanthropus

Orrorin

Ardipithecus

Australopithecus

Homo habilis

Homo erectus

H. heidelbergensis

Homo sapiens

Neanderthals

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Earlier apes

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Gorilla split

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Chimpanzee split

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Earliest bipedal

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Stone tools

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Expansion beyond Africa

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Earliest fire use

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Earliest cooking

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Modern humans

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The taxonomic relationships of hominoids.

Biologists classify humans, along with only a few other species, as great apes (species in the family Hominidae). The living Hominidae include two distinct species of chimpanzee (the bonobo, Pan paniscus, and the common chimpanzee, Pan troglodytes), two species of gorilla (the western gorilla, Gorilla gorilla, and the eastern gorilla, Gorilla graueri), and two species of orangutan (the Bornean orangutan, Pongo pygmaeus, and the Sumatran orangutan, Pongo abelii). The great apes with the family Hylobatidae of gibbons form the superfamily Hominoidea of apes.

Apes, in turn, belong to the primate order (>400 species), along with the Old World monkeys, the New World monkeys, and others. Data from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) indicate that primates belong to the group of Euarchontoglires, together with Rodentia, Lagomorpha, Dermoptera, and Scandentia. This is further supported by Alu-like short interspersed nuclear elements (SINEs) which have been found only in members of the Euarchontoglires.

Phylogenetics

A phylogenetic tree is usually derived from DNA or protein sequences from populations. Often, mitochondrial DNA or Y chromosome sequences are used to study ancient human demographics. These single-locus sources of DNA do not recombine and are almost always inherited from a single parent, with only one known exception in mtDNA. Individuals from closer geographic regions generally tend to be more similar than individuals from regions farther away. Distance on a phylogenetic tree can be used approximately to indicate:

1. Genetic distance. The genetic difference between humans and chimpanzees is less than 2%, or three times larger than the variation among modern humans (estimated at 0.6%).
2. Temporal remoteness of the most recent common ancestor. The mitochondrial most recent common ancestor of modern humans is estimated to have lived roughly 160,000 years ago, the latest common ancestors of humans and chimpanzees roughly 5 to 6 million years ago.

Speciation of humans and the African apes

The separation of humans from their closest relatives, the non-human apes (chimpanzees and gorillas), has been studied extensively for more than a century. Five major questions have been addressed:

• Which apes are our closest ancestors?
• When did the separations occur?
• What was the effective population size of the common ancestor before the split?
• Are there traces of population structure (subpopulations) preceding the speciation or partial admixture succeeding it?
• What were the specific events (including fusion of chromosomes 2a and 2b) prior to and subsequent to the separation?

General observations

As discussed before, different parts of the genome show different sequence divergence between different hominoids. It has also been shown that the sequence divergence between DNA from humans and chimpanzees varies greatly. For example, the sequence divergence varies between 0% to 2.66% between non-coding, non-repetitive genomic regions of humans and chimpanzees. The percentage of nucleotides in the human genome (hg38) that had one-to-one exact matches in the chimpanzee genome (pantro6) was 84.38%. Additionally gene trees, generated by comparative analysis of DNA segments, do not always fit the species tree. Summing up:

• The sequence divergence varies significantly between humans, chimpanzees and gorillas.
• For most DNA sequences, humans and chimpanzees appear to be most closely related, but some point to a human-gorilla or chimpanzee-gorilla clade.
• The human genome has been sequenced, as well as the chimpanzee genome. Humans have 23 pairs of chromosomes, while chimpanzees, gorillas and orangutans have 24. Human chromosome 2 is a fusion of two chromosomes 2a and 2b that remained separate in the other primates.

Divergence times

The divergence time of humans from other apes is of great interest. One of the first molecular studies, published in 1967 measured immunological distances (IDs) between different primates. Basically the study measured the strength of immunological response that an antigen from one species (human albumin) induces in the immune system of another species (human, chimpanzee, gorilla and Old World monkeys). Closely related species should have similar antigens and therefore weaker immunological response to each other's antigens. The immunological response of a species to its own antigens (e.g. human to human) was set to be 1.

The ID between humans and gorillas was determined to be 1.09, that between humans and chimpanzees was determined as 1.14. However the distance to six different Old World monkeys was on average 2.46, indicating that the African apes are more closely related to humans than to monkeys. The authors consider the divergence time between Old World monkeys and hominoids to be 30 million years ago (MYA), based on fossil data, and the immunological distance was considered to grow at a constant rate. They concluded that divergence time of humans and the African apes to be roughly ~5 MYA. That was a surprising result. Most scientists at that time thought that humans and great apes diverged much earlier (>15 MYA).

The gorilla was, in ID terms, closer to human than to chimpanzees; however, the difference was so slight that the trichotomy could not be resolved with certainty. Later studies based on molecular genetics were able to resolve the trichotomy: chimpanzees are phylogenetically closer to humans than to gorillas. However, some divergence times estimated later (using much more sophisticated methods in molecular genetics) do not substantially differ from the very first estimate in 1967, but a recent paper puts it at 11–14 MYA.

Divergence times and ancestral effective population size

The sequences of the DNA segments diverge earlier than the species. A large effective population size in the ancestral population (left) preserves different variants of the DNA segments (=alleles) for a longer period of time. Therefore, on average, the gene divergence times (t_A for DNA segment A; t_B for DNA segment B) will deviate more from the time the species diverge (t_S) compared to a small ancestral effective population size (right).

Current methods to determine divergence times use DNA sequence alignments and molecular clocks. Usually the molecular clock is calibrated assuming that the orangutan split from the African apes (including humans) 12-16 MYA. Some studies also include some old world monkeys and set the divergence time of them from hominoids to 25-30 MYA. Both calibration points are based on very little fossil data and have been criticized.

If these dates are revised, the divergence times estimated from molecular data will change as well. However, the relative divergence times are unlikely to change. Even if we can't tell absolute divergence times exactly, we can be pretty sure that the divergence time between chimpanzees and humans is about sixfold shorter than between chimpanzees (or humans) and monkeys.

One study (Takahata et al., 1995) used 15 DNA sequences from different regions of the genome from human and chimpanzee and 7 DNA sequences from human, chimpanzee and gorilla. They determined that chimpanzees are more closely related to humans than gorillas. Using various statistical methods, they estimated the divergence time human-chimp to be 4.7 MYA and the divergence time between gorillas and humans (and chimps) to be 7.2 MYA.

Additionally they estimated the effective population size of the common ancestor of humans and chimpanzees to be ~100,000. This was somewhat surprising since the present day effective population size of humans is estimated to be only ~10,000. If true that means that the human lineage would have experienced an immense decrease of its effective population size (and thus genetic diversity) in its evolution.

A and B are two different loci. In the upper figure they fit to the species tree. The DNA that is present in today's gorillas diverged earlier from the DNA that is present in today's humans and chimps. Thus both loci should be more similar between human and chimp than between gorilla and chimp or gorilla and human. In the lower graph, locus A has a more recent common ancestor in human and gorilla compared to the chimp sequence. Whereas chimp and gorilla have a more recent common ancestor for locus B. Here the gene trees are incongruent to the species tree.

Another study (Chen & Li, 2001) sequenced 53 non-repetitive, intergenic DNA segments from human, chimpanzee, gorilla and orangutan. When the DNA sequences were concatenated to a single long sequence, the generated neighbor-joining tree supported the Homo-Pan clade with 100% bootstrap (that is that humans and chimpanzees are the closest related species of the four). When three species are fairly closely related to each other (like human, chimpanzee and gorilla), the trees obtained from DNA sequence data may not be congruent with the tree that represents the speciation (species tree).

The shorter internodal time span (T_IN) the more common are incongruent gene trees. The effective population size (N_e) of the internodal population determines how long genetic lineages are preserved in the population. A higher effective population size causes more incongruent gene trees. Therefore, if the internodal time span is known, the ancestral effective population size of the common ancestor of humans and chimpanzees can be calculated.

When each segment was analyzed individually, 31 supported the Homo-Pan clade, 10 supported the Homo-Gorilla clade, and 12 supported the Pan-Gorilla clade. Using the molecular clock the authors estimated that gorillas split up first 6.2-8.4 MYA and chimpanzees and humans split up 1.6-2.2 million years later (internodal time span) 4.6-6.2 MYA. The internodal time span is useful to estimate the ancestral effective population size of the common ancestor of humans and chimpanzees.

A parsimonious analysis revealed that 24 loci supported the Homo-Pan clade, 7 supported the Homo-Gorilla clade, 2 supported the Pan-Gorilla clade and 20 gave no resolution. Additionally they took 35 protein coding loci from databases. Of these 12 supported the Homo-Pan clade, 3 the Homo-Gorilla clade, 4 the Pan-Gorilla clade and 16 gave no resolution. Therefore, only ~70% of the 52 loci that gave a resolution (33 intergenic, 19 protein coding) support the 'correct' species tree. From the fraction of loci which did not support the species tree and the internodal time span they estimated previously, the effective population of the common ancestor of humans and chimpanzees was estimated to be ~52 000 to 96 000. This value is not as high as that from the first study (Takahata), but still much higher than present day effective population size of humans.

A third study (Yang, 2002) used the same dataset that Chen and Li used but estimated the ancestral effective population of 'only' ~12,000 to 21,000, using a different statistical method.

Genetic differences between humans and other great apes

The alignable sequences within genomes of humans and chimpanzees differ by about 35 million single-nucleotide substitutions. Additionally about 3% of the complete genomes differ by deletions, insertions and duplications.

Since mutation rate is relatively constant, roughly one half of these changes occurred in the human lineage. Only a very tiny fraction of those fixed differences gave rise to the different phenotypes of humans and chimpanzees and finding those is a great challenge. The vast majority of the differences are neutral and do not affect the phenotype.

Molecular evolution may act in different ways, through protein evolution, gene loss, differential gene regulation and RNA evolution. All are thought to have played some part in human evolution.

Gene loss

Many different mutations can inactivate a gene, but few will change its function in a specific way. Inactivation mutations will therefore be readily available for selection to act on. Gene loss could thus be a common mechanism of evolutionary adaptation (the "less-is-more" hypothesis).

80 genes were lost in the human lineage after separation from the last common ancestor with the chimpanzee. 36 of those were for olfactory receptors. Genes involved in chemoreception and immune response are overrepresented. Another study estimated that 86 genes had been lost.

Hair keratin gene KRTHAP1

A gene for type I hair keratin was lost in the human lineage. Keratins are a major component of hairs. Humans still have nine functional type I hair keratin genes, but the loss of that particular gene may have caused the thinning of human body hair. Based on the assumption of a constant molecular clock, the study predicts the gene loss occurred relatively recently in human evolution—less than 240 000 years ago, but both the Vindija Neandertal and the high-coverage Denisovan sequence contain the same premature stop codons as modern humans and hence dating should be greater than 750 000 years ago. 

Myosin gene MYH16

Stedman et al. (2004) stated that the loss of the sarcomeric myosin gene MYH16 in the human lineage led to smaller masticatory muscles. They estimated that the mutation that led to the inactivation (a two base pair deletion) occurred 2.4 million years ago, predating the appearance of Homo ergaster/erectus in Africa. The period that followed was marked by a strong increase in cranial capacity, promoting speculation that the loss of the gene may have removed an evolutionary constraint on brain size in the genus Homo.

Another estimate for the loss of the MYH16 gene is 5.3 million years ago, long before Homo appeared.

Other

• CASPASE12, a cysteinyl aspartate proteinase. The loss of this gene is speculated to have reduced the lethality of bacterial infection in humans.

Gene addition

Segmental duplications (SDs or LCRs) have had roles in creating new primate genes and shaping human genetic variation.

Human-specific DNA insertions

When the human genome was compared to the genomes of five comparison primate species, including the chimpanzee, gorilla, orangutan, gibbon, and macaque, it was found that there are approximately 20,000 human-specific insertions believed to be regulatory. While most insertions appear to be fitness neutral, a small amount have been identified in positively selected genes showing associations to neural phenotypes and some relating to dental and sensory perception-related phenotypes. These findings hint at the seemingly important role of human-specific insertions in the recent evolution of humans.

Selection pressures

Human accelerated regions are areas of the genome that differ between humans and chimpanzees to a greater extent than can be explained by genetic drift over the time since the two species shared a common ancestor. These regions show signs of being subject to natural selection, leading to the evolution of distinctly human traits. Two examples are HAR1F, which is believed to be related to brain development and HAR2 (a.k.a. HACNS1) that may have played a role in the development of the opposable thumb.

It has also been hypothesized that much of the difference between humans and chimpanzees is attributable to the regulation of gene expression rather than differences in the genes themselves. Analyses of conserved non-coding sequences, which often contain functional and thus positively selected regulatory regions, address this possibility.

Sequence divergence between humans and apes

When the draft sequence of the common chimpanzee (Pan troglodytes) genome was published in the summer 2005, 2400 million bases (of ~3160 million bases) were sequenced and assembled well enough to be compared to the human genome. 1.23% of this sequenced differed by single-base substitutions. Of this, 1.06% or less was thought to represent fixed differences between the species, with the rest being variant sites in humans or chimpanzees. Another type of difference, called indels (insertions/deletions) accounted for many fewer differences (15% as many), but contributed ~1.5% of unique sequence to each genome, since each insertion or deletion can involve anywhere from one base to millions of bases.

A companion paper examined segmental duplications in the two genomes, whose insertion and deletion into the genome account for much of the indel sequence. They found that a total of 2.7% of euchromatic sequence had been differentially duplicated in one or the other lineage.

Percentage sequence divergence between humans and other hominids

Locus	Human-Chimp	Human-Gorilla	Human-Orangutan
Alu elements	2	-	-
Non-coding (Chr. Y)	1.68 ± 0.19	2.33 ± 0.2	5.63 ± 0.35
Pseudogenes (autosomal)	1.64 ± 0.10	1.87 ± 0.11	-
Pseudogenes (Chr. X)	1.47 ± 0.17	-	-
Noncoding (autosomal)	1.24 ± 0.07	1.62 ± 0.08	3.08 ± 0.11
Genes (Ks)	1.11	1.48	2.98
Introns	0.93 ± 0.08	1.23 ± 0.09	-
Xq13.3	0.92 ± 0.10	1.42 ± 0.12	3.00 ± 0.18
Subtotal for X chromosome	1.16 ± 0.07	1.47 ± 0.08	-
Genes (Ka)	0.8	0.93	1.96

The sequence divergence has generally the following pattern: Human-Chimp < Human-Gorilla << Human-Orangutan, highlighting the close kinship between humans and the African apes. Alu elements diverge quickly due to their high frequency of CpG dinucleotides which mutate roughly 10 times more often than the average nucleotide in the genome. The mutation rate is higher in the male germ line, therefore the divergence in the Y chromosome—which is inherited solely from the father—is higher than in autosomes. The X chromosome is inherited twice as often through the female germ line as through the male germ line and therefore shows slightly lower sequence divergence. The sequence divergence of the Xq13.3 region is surprisingly low between humans and chimpanzees.

Mutations altering the amino acid sequence of proteins (K_a) are the least common. In fact ~29% of all orthologous proteins are identical between human and chimpanzee. The typical protein differs by only two amino acids. The measures of sequence divergence shown in the table only take the substitutional differences, for example from an A (adenine) to a G (guanine), into account. DNA sequences may however also differ by insertions and deletions (indels) of bases. These are usually stripped from the alignments before the calculation of sequence divergence is performed.

Genetic differences between modern humans and Neanderthals

An international group of scientists completed a draft sequence of the Neanderthal genome in May 2010. The results indicate some breeding between modern humans (Homo sapiens) and Neanderthals (Homo neanderthalensis), as the genomes of non-African humans have 1–4% more in common with Neanderthals than do the genomes of subsaharan Africans. Neanderthals and most modern humans share a lactose-intolerant variant of the lactase gene that encodes an enzyme that is unable to break down lactose in milk after weaning. Modern humans and Neanderthals also share the FOXP2 gene variant associated with brain development and with speech in modern humans, indicating that Neanderthals may have been able to speak. Chimps have two amino acid differences in FOXP2 compared with human and Neanderthal FOXP2.

Genetic differences among modern humans

H. sapiens is thought to have emerged about 300,000 years ago. It dispersed throughout Africa, and after 70,000 years ago throughout Eurasia and Oceania. A 2009 study identified 14 "ancestral population clusters", the most remote being the San people of Southern Africa.

With their rapid expansion throughout different climate zones, and especially with the availability of new food sources with the domestication of cattle and the development of agriculture, human populations have been exposed to significant selective pressures since their dispersal. For example, East Asians have been found to be separated from Europids by a number of concentrated alleles suggestive of selection pressures, including variants of the EDAR, ADH1B, ABCC1, and ALDH2genes. The East Asian types of ADH1B in particular are associated with rice domestication and would thus have arisen after the development of rice cultivation roughly 10,000 years ago. Several phenotypical traits of characteristic of East Asians are due to a single mutation of the EDAR gene, dated to c. 35,000 years ago.

As of 2017, the Single Nucleotide Polymorphism Database (dbSNP), which lists SNP and other variants, listed a total of 324 million variants found in sequenced human genomes. Nucleotide diversity, the average proportion of nucleotides that differ between two individuals, is estimated at between 0.1% and 0.4% for contemporary humans (compared to 2% between humans and chimpanzees). This corresponds to genome differences at a few million sites; the 1000 Genomes Project similarly found that "a typical [individual] genome differs from the reference human genome at 4.1 million to 5.0 million sites … affecting 20 million bases of sequence."

In February 2019, scientists discovered evidence, based on genetics studies using artificial intelligence (AI), that suggest the existence of an unknown human ancestor species, not Neanderthal, Denisovan or human hybrid (like Denny (hybrid hominin)), in the genome of modern humans.

Research studies

In March 2019, Chinese scientists reported inserting the human brain-related MCPH1 gene into laboratory rhesus monkeys, resulting in the transgenic monkeys performing better and answering faster on "short-term memory tests involving matching colors and shapes", compared to control non-transgenic monkeys, according to the researchers.

Human genetic variation

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Human_genetic_variation 

 

A graphical representation of the typical human karyotype.

 

The human mitochondrial DNA.

Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism.

No two humans are genetically identical. Even monozygotic twins (who develop from one zygote) have infrequent genetic differences due to mutations occurring during development and gene copy-number variation. Differences between individuals, even closely related individuals, are the key to techniques such as genetic fingerprinting. As of 2017, there are a total of 324 million known variants from sequenced human genomes. As of 2015, the typical difference between an individual's genome and the reference genome was estimated at 20 million base pairs (or 0.6% of the total of 3.2 billion base pairs).

Alleles occur at different frequencies in different human populations. Populations that are more geographically and ancestrally remote tend to differ more. The differences between populations represent a small proportion of overall human genetic variation. Populations also differ in the quantity of variation among their members. The greatest divergence between populations is found in sub-Saharan Africa, consistent with the recent African origin of non-African populations. Populations also vary in the proportion and locus of introgressed genes they received by archaic admixture both inside and outside of Africa.

The study of human genetic variation has evolutionary significance and medical applications. It can help scientists understand ancient human population migrations as well as how human groups are biologically related to one another. For medicine, study of human genetic variation may be important because some disease-causing alleles occur more often in people from specific geographic regions. New findings show that each human has on average 60 new mutations compared to their parents.

Causes of variation

Causes of differences between individuals include independent assortment, the exchange of genes (crossing over and recombination) during reproduction (through meiosis) and various mutational events.

There are at least three reasons why genetic variation exists between populations. Natural selection may confer an adaptive advantage to individuals in a specific environment if an allele provides a competitive advantage. Alleles under selection are likely to occur only in those geographic regions where they confer an advantage. A second important process is genetic drift, which is the effect of random changes in the gene pool, under conditions where most mutations are neutral (that is, they do not appear to have any positive or negative selective effect on the organism). Finally, small migrant populations have statistical differences - called the founder effect - from the overall populations where they originated; when these migrants settle new areas, their descendant population typically differs from their population of origin: different genes predominate and it is less genetically diverse.

In humans, the main cause is genetic drift. Serial founder effects and past small population size (increasing the likelihood of genetic drift) may have had an important influence in neutral differences between populations. The second main cause of genetic variation is due to the high degree of neutrality of most mutations. A small, but significant number of genes appear to have undergone recent natural selection, and these selective pressures are sometimes specific to one region.

Measures of variation

Genetic variation among humans occurs on many scales, from gross alterations in the human karyotype to single nucleotide changes. Chromosome abnormalities are detected in 1 of 160 live human births. Apart from sex chromosome disorders, most cases of aneuploidy result in death of the developing fetus (miscarriage); the most common extra autosomal chromosomes among live births are 21, 18 and 13.

Nucleotide diversity is the average proportion of nucleotides that differ between two individuals. As of 2004, the human nucleotide diversity was estimated to be 0.1% to 0.4% of base pairs. In 2015, the 1000 Genomes Project, which sequenced one thousand individuals from 26 human populations, found that "a typical [individual] genome differs from the reference human genome at 4.1 million to 5.0 million sites … affecting 20 million bases of sequence"; the latter figure corresponds to 0.6% of total number of base pairs. Nearly all (>99.9%) of these sites are small differences, either single nucleotide polymorphisms or brief insertions or deletions (indels) in the genetic sequence, but structural variations account for a greater number of base-pairs than the SNPs and indels.

As of 2017, the Single Nucleotide Polymorphism Database (dbSNP), which lists SNP and other variants, listed 324 million variants found in sequenced human genomes.

Single nucleotide polymorphisms

DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism).

A single nucleotide polymorphism (SNP) is a difference in a single nucleotide between members of one species that occurs in at least 1% of the population. The 2,504 individuals characterized by the 1000 Genomes Project had 84.7 million SNPs among them. SNPs are the most common type of sequence variation, estimated in 1998 to account for 90% of all sequence variants. Other sequence variations are single base exchanges, deletions and insertions. SNPs occur on average about every 100 to 300 bases and so are the major source of heterogeneity.

A functional, or non-synonymous, SNP is one that affects some factor such as gene splicing or messenger RNA, and so causes a phenotypic difference between members of the species. About 3% to 5% of human SNPs are functional (see International HapMap Project). Neutral, or synonymous SNPs are still useful as genetic markers in genome-wide association studies, because of their sheer number and the stable inheritance over generations.

A coding SNP is one that occurs inside a gene. There are 105 Human Reference SNPs that result in premature stop codons in 103 genes. This corresponds to 0.5% of coding SNPs. They occur due to segmental duplication in the genome. These SNPs result in loss of protein, yet all these SNP alleles are common and are not purified in negative selection.

Structural variation

Structural variation is the variation in structure of an organism's chromosome. Structural variations, such as copy-number variation and deletions, inversions, insertions and duplications, account for much more human genetic variation than single nucleotide diversity. This was concluded in 2007 from analysis of the diploid full sequences of the genomes of two humans: Craig Venter and James D. Watson. This added to the two haploid sequences which were amalgamations of sequences from many individuals, published by the Human Genome Project and Celera Genomics respectively.

According to the 1000 Genomes Project, a typical human has 2,100 to 2,500 structural variations, which include approximately 1,000 large deletions, 160 copy-number variants, 915 Alu insertions, 128 L1 insertions, 51 SVA insertions, 4 NUMTs, and 10 inversions.

Copy number variation

A copy-number variation (CNV) is a difference in the genome due to deleting or duplicating large regions of DNA on some chromosome. It is estimated that 0.4% of the genomes of unrelated humans differ with respect to copy number. When copy number variation is included, human-to-human genetic variation is estimated to be at least 0.5% (99.5% similarity). Copy number variations are inherited but can also arise during development.

A visual map with the regions with high genomic variation of the modern-human reference assembly relatively to a Neanderthal of 50k has been built by Pratas et al.

Epigenetics

Epigenetic variation is variation in the chemical tags that attach to DNA and affect how genes get read. The tags, "called epigenetic markings, act as switches that control how genes can be read." At some alleles, the epigenetic state of the DNA, and associated phenotype, can be inherited across generations of individuals.

Genetic variability

Genetic variability is a measure of the tendency of individual genotypes in a population to vary (become different) from one another. Variability is different from genetic diversity, which is the amount of variation seen in a particular population. The variability of a trait is how much that trait tends to vary in response to environmental and genetic influences.

Clines

In biology, a cline is a continuum of species, populations, varieties, or forms of organisms that exhibit gradual phenotypic and/or genetic differences over a geographical area, typically as a result of environmental heterogeneity. In the scientific study of human genetic variation, a gene cline can be rigorously defined and subjected to quantitative metrics.

Haplogroups

In the study of molecular evolution, a haplogroup is a group of similar haplotypes that share a common ancestor with a single nucleotide polymorphism (SNP) mutation. The study of haplogroups provides information about ancestral origins dating back thousands of years.

The most commonly studied human haplogroups are Y-chromosome (Y-DNA) haplogroups and mitochondrial DNA (mtDNA) haplogroups, both of which can be used to define genetic populations. Y-DNA is passed solely along the patrilineal line, from father to son, while mtDNA is passed down the matrilineal line, from mother to both daughter or son. The Y-DNA and mtDNA may change by chance mutation at each generation.

Variable number tandem repeats

A variable number tandem repeat (VNTR) is the variation of length of a tandem repeat. A tandem repeat is the adjacent repetition of a short nucleotide sequence. Tandem repeats exist on many chromosomes, and their length varies between individuals. Each variant acts as an inherited allele, so they are used for personal or parental identification. Their analysis is useful in genetics and biology research, forensics, and DNA fingerprinting.

Short tandem repeats (about 5 base pairs) are called microsatellites, while longer ones are called minisatellites.

History and geographic distribution

Map of the migration of modern humans out of Africa, based on mitochondrial DNA. Colored rings indicate thousand years before present.

 

Genetic distance map by Magalhães et al. (2012)

Recent African origin of modern humans

The recent African origin of modern humans paradigm assumes the dispersal of non-African populations of anatomically modern humans after 70,000 years ago. Dispersal within Africa occurred significantly earlier, at least 130,000 years ago. The "out of Africa" theory originates in the 19th century, as a tentative suggestion in Charles Darwin's Descent of Man, but remained speculative until the 1980s when it was supported by the study of present-day mitochondrial DNA, combined with evidence from physical anthropology of archaic specimens.

According to a 2000 study of Y-chromosome sequence variation, human Y-chromosomes trace ancestry to Africa, and the descendants of the derived lineage left Africa and eventually were replaced by archaic human Y-chromosomes in Eurasia. The study also shows that a minority of contemporary populations in East Africa and the Khoisan are the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa 35,000 to 89,000 years ago. Other evidence supporting the theory is that variations in skull measurements decrease with distance from Africa at the same rate as the decrease in genetic diversity. Human genetic diversity decreases in native populations with migratory distance from Africa, and this is thought to be due to bottlenecks during human migration, which are events that temporarily reduce population size.

A 2009 genetic clustering study, which genotyped 1327 polymorphic markers in various African populations, identified six ancestral clusters. The clustering corresponded closely with ethnicity, culture and language. A 2018 whole genome sequencing study of the world's populations observed similar clusters among the populations in Africa. At K=9, distinct ancestral components defined the Afroasiatic-speaking populations inhabiting North Africa and Northeast Africa; the Nilo-Saharan-speaking populations in Northeast Africa and East Africa; the Ari populations in Northeast Africa; the Niger-Congo-speaking populations in West-Central Africa, West Africa, East Africa and Southern Africa; the Pygmy populations in Central Africa; and the Khoisan populations in Southern Africa.

Population genetics

Because of the common ancestry of all humans, only a small number of variants have large differences in frequency between populations. However, some rare variants in the world's human population are much more frequent in at least one population (more than 5%).

Genetic variation

It is commonly assumed that early humans left Africa, and thus must have passed through a population bottleneck before their African-Eurasian divergence around 100,000 years ago (ca. 3,000 generations). The rapid expansion of a previously small population has two important effects on the distribution of genetic variation. First, the so-called founder effect occurs when founder populations bring only a subset of the genetic variation from their ancestral population. Second, as founders become more geographically separated, the probability that two individuals from different founder populations will mate becomes smaller. The effect of this assortative mating is to reduce gene flow between geographical groups and to increase the genetic distance between groups.

The expansion of humans from Africa affected the distribution of genetic variation in two other ways. First, smaller (founder) populations experience greater genetic drift because of increased fluctuations in neutral polymorphisms. Second, new polymorphisms that arose in one group were less likely to be transmitted to other groups as gene flow was restricted.

Populations in Africa tend to have lower amounts of linkage disequilibrium than do populations outside Africa, partly because of the larger size of human populations in Africa over the course of human history and partly because the number of modern humans who left Africa to colonize the rest of the world appears to have been relatively low. In contrast, populations that have undergone dramatic size reductions or rapid expansions in the past and populations formed by the mixture of previously separate ancestral groups can have unusually high levels of linkage disequilibrium

Distribution of variation

Human genetic variation calculated from genetic data representing 346 microsatellite loci taken from 1484 individuals in 78 human populations. The upper graph illustrates that as populations are further from East Africa, they have declining genetic diversity as measured in average number of microsatellite repeats at each of the loci. The bottom chart illustrates isolation by distance. Populations with a greater distance between them are more dissimilar (as measured by the Fst statistic) than those which are geographically close to one another. The horizontal axis of both charts is geographic distance as measured along likely routes of human migration. (Chart from Kanitz et al. 2018)

The distribution of genetic variants within and among human populations are impossible to describe succinctly because of the difficulty of defining a "population," the clinal nature of variation, and heterogeneity across the genome (Long and Kittles 2003). In general, however, an average of 85% of genetic variation exists within local populations, ~7% is between local populations within the same continent, and ~8% of variation occurs between large groups living on different continents. The recent African origin theory for humans would predict that in Africa there exists a great deal more diversity than elsewhere and that diversity should decrease the further from Africa a population is sampled.

Phenotypic variation

Sub-Saharan Africa has the most human genetic diversity and the same has been shown to hold true for phenotypic variation in skull form. Phenotype is connected to genotype through gene expression. Genetic diversity decreases smoothly with migratory distance from that region, which many scientists believe to be the origin of modern humans, and that decrease is mirrored by a decrease in phenotypic variation. Skull measurements are an example of a physical attribute whose within-population variation decreases with distance from Africa.

The distribution of many physical traits resembles the distribution of genetic variation within and between human populations (American Association of Physical Anthropologists 1996; Keita and Kittles 1997). For example, ~90% of the variation in human head shapes occurs within continental groups, and ~10% separates groups, with a greater variability of head shape among individuals with recent African ancestors (Relethford 2002).

A prominent exception to the common distribution of physical characteristics within and among groups is skin color. Approximately 10% of the variance in skin color occurs within groups, and ~90% occurs between groups (Relethford 2002). This distribution of skin color and its geographic patterning — with people whose ancestors lived predominantly near the equator having darker skin than those with ancestors who lived predominantly in higher latitudes — indicate that this attribute has been under strong selective pressure. Darker skin appears to be strongly selected for in equatorial regions to prevent sunburn, skin cancer, the photolysis of folate, and damage to sweat glands.

Understanding how genetic diversity in the human population impacts various levels of gene expression is an active area of research. While earlier studies focused on the relationship between DNA variation and RNA expression, more recent efforts are characterizing the genetic control of various aspects of gene expression including chromatin states, translation, and protein levels. A study published in 2007 found that 25% of genes showed different levels of gene expression between populations of European and Asian descent. The primary cause of this difference in gene expression was thought to be SNPs in gene regulatory regions of DNA. Another study published in 2007 found that approximately 83% of genes were expressed at different levels among individuals and about 17% between populations of European and African descent.

Wright's Fixation index as measure of variation

The population geneticist Sewall Wright developed the fixation index (often abbreviated to F_ST) as a way of measuring genetic differences between populations. This statistic is often used in taxonomy to compare differences between any two given populations by measuring the genetic differences among and between populations for individual genes, or for many genes simultaneously. It is often stated that the fixation index for humans is about 0.15. This translates to an estimated 85% of the variation measured in the overall human population is found within individuals of the same population, and about 15% of the variation occurs between populations. These estimates imply that any two individuals from different populations are almost as likely to be more similar to each other than either is to a member of their own group. "The shared evolutionary history of living humans has resulted in a high relatedness among all living people, as indicated for example by the very low fixation index (F_ST) among living human populations." Richard Lewontin, who affirmed these ratios, thus concluded neither "race" nor "subspecies" were appropriate or useful ways to describe human populations.

Wright himself believed that values >0.25 represent very great genetic variation and that an F_ST of 0.15–0.25 represented great variation. However, about 5% of human variation occurs between populations within continents, therefore F_ST values between continental groups of humans (or races) of as low as 0.1 (or possibly lower) have been found in some studies, suggesting more moderate levels of genetic variation. Graves (1996) has countered that F_ST should not be used as a marker of subspecies status, as the statistic is used to measure the degree of differentiation between populations, although see also Wright (1978).

Jeffrey Long and Rick Kittles give a long critique of the application of F_ST to human populations in their 2003 paper "Human Genetic Diversity and the Nonexistence of Biological Races". They find that the figure of 85% is misleading because it implies that all human populations contain on average 85% of all genetic diversity. They argue the underlying statistical model incorrectly assumes equal and independent histories of variation for each large human population. A more realistic approach is to understand that some human groups are parental to other groups and that these groups represent paraphyletic groups to their descent groups. For example, under the recent African origin theory the human population in Africa is paraphyletic to all other human groups because it represents the ancestral group from which all non-African populations derive, but more than that, non-African groups only derive from a small non-representative sample of this African population. This means that all non-African groups are more closely related to each other and to some African groups (probably east Africans) than they are to others, and further that the migration out of Africa represented a genetic bottleneck, with much of the diversity that existed in Africa not being carried out of Africa by the emigrating groups. Under this scenario, human populations do not have equal amounts of local variability, but rather diminished amounts of diversity the further from Africa any population lives. Long and Kittles find that rather than 85% of human genetic diversity existing in all human populations, about 100% of human diversity exists in a single African population, whereas only about 70% of human genetic diversity exists in a population derived from New Guinea. Long and Kittles argued that this still produces a global human population that is genetically homogeneous compared to other mammalian populations.

Archaic admixture

There is a hypothesis that anatomically modern humans interbred with Neanderthals during the Middle Paleolithic. In May 2010, the Neanderthal Genome Project presented genetic evidence that interbreeding did likely take place and that a small but significant portion, around 2-4%, of Neanderthal admixture is present in the DNA of modern Eurasians and Oceanians, and nearly absent in sub-Saharan African populations.

Between 4% and 6% of the genome of Melanesians (represented by the Papua New Guinean and Bougainville Islander) are thought to derive from Denisova hominins – a previously unknown species which shares a common origin with Neanderthals. It was possibly introduced during the early migration of the ancestors of Melanesians into Southeast Asia. This history of interaction suggests that Denisovans once ranged widely over eastern Asia.

Thus, Melanesians emerge as the most archaic-admixed population, having Denisovan/Neanderthal-related admixture of ~8%.

In a study published in 2013, Jeffrey Wall from University of California studied whole sequence-genome data and found higher rates of introgression in Asians compared to Europeans. Hammer et al. tested the hypothesis that contemporary African genomes have signatures of gene flow with archaic human ancestors and found evidence of archaic admixture in the genomes of some African groups, suggesting that modest amounts of gene flow were widespread throughout time and space during the evolution of anatomically modern humans.

Categorization of the world population

Chart showing human genetic clustering.

New data on human genetic variation has reignited the debate about a possible biological basis for categorization of humans into races. Most of the controversy surrounds the question of how to interpret the genetic data and whether conclusions based on it are sound. Some researchers argue that self-identified race can be used as an indicator of geographic ancestry for certain health risks and medications.

Although the genetic differences among human groups are relatively small, these differences in certain genes such as duffy, ABCC11, SLC24A5, called ancestry-informative markers (AIMs) nevertheless can be used to reliably situate many individuals within broad, geographically based groupings. For example, computer analyses of hundreds of polymorphic loci sampled in globally distributed populations have revealed the existence of genetic clustering that roughly is associated with groups that historically have occupied large continental and subcontinental regions (Rosenberg et al. 2002; Bamshad et al. 2003).

Some commentators have argued that these patterns of variation provide a biological justification for the use of traditional racial categories. They argue that the continental clusterings correspond roughly with the division of human beings into sub-Saharan Africans; Europeans, Western Asians, Central Asians, Southern Asians and Northern Africans; Eastern Asians, Southeast Asians, Polynesians and Native Americans; and other inhabitants of Oceania (Melanesians, Micronesians & Australian Aborigines) (Risch et al. 2002). Other observers disagree, saying that the same data undercut traditional notions of racial groups (King and Motulsky 2002; Calafell 2003; Tishkoff and Kidd 2004). They point out, for example, that major populations considered races or subgroups within races do not necessarily form their own clusters.

Furthermore, because human genetic variation is clinal, many individuals affiliate with two or more continental groups. Thus, the genetically based "biogeographical ancestry" assigned to any given person generally will be broadly distributed and will be accompanied by sizable uncertainties (Pfaff et al. 2004).

In many parts of the world, groups have mixed in such a way that many individuals have relatively recent ancestors from widely separated regions. Although genetic analyses of large numbers of loci can produce estimates of the percentage of a person's ancestors coming from various continental populations (Shriver et al. 2003; Bamshad et al. 2004), these estimates may assume a false distinctiveness of the parental populations, since human groups have exchanged mates from local to continental scales throughout history (Cavalli-Sforza et al. 1994; Hoerder 2002). Even with large numbers of markers, information for estimating admixture proportions of individuals or groups is limited, and estimates typically will have wide confidence intervals (Pfaff et al. 2004).

Genetic clustering

Genetic data can be used to infer population structure and assign individuals to groups that often correspond with their self-identified geographical ancestry. Jorde and Wooding (2004) argued that "Analysis of many loci now yields reasonably accurate estimates of genetic similarity among individuals, rather than populations. Clustering of individuals is correlated with geographic origin or ancestry." However, identification by geographic origin may quickly break down when considering historical ancestry shared between individuals back in time.

An analysis of autosomal SNP data from the International HapMap Project (Phase II) and CEPH Human Genome Diversity Panel samples was published in 2009. The study of 53 populations taken from the HapMap and CEPH data (1138 unrelated individuals) suggested that natural selection may shape the human genome much more slowly than previously thought, with factors such as migration within and among continents more heavily influencing the distribution of genetic variations. A similar study published in 2010 found strong genome-wide evidence for selection due to changes in ecoregion, diet, and subsistence particularly in connection with polar ecoregions, with foraging, and with a diet rich in roots and tubers. In a 2016 study, principal component analysis of genome-wide data was capable of recovering previously-known targets for positive selection (without prior definition of populations) as well as a number of new candidate genes.

Forensic anthropology

Forensic anthropologists can assess the ancestry of skeletal remains by analyzing skeletal morphology as well as using genetic and chemical markers, when possible. While these assessments are never certain, the accuracy of skeletal morphology analyses in determining true ancestry has been estimated at about 90%.

Ternary plot showing average admixture of five North American ethnic groups. Individuals that self-identify with each group can be found at many locations on the map, but on average groups tend to cluster differently.

Gene flow and admixture

Gene flow between two populations reduces the average genetic distance between the populations, only totally isolated human populations experience no gene flow and most populations have continuous gene flow with other neighboring populations which create the clinal distribution observed for moth genetic variation. When gene flow takes place between well-differentiated genetic populations the result is referred to as "genetic admixture".

Admixture mapping is a technique used to study how genetic variants cause differences in disease rates between population. Recent admixture populations that trace their ancestry to multiple continents are well suited for identifying genes for traits and diseases that differ in prevalence between parental populations. African-American populations have been the focus of numerous population genetic and admixture mapping studies, including studies of complex genetic traits such as white cell count, body-mass index, prostate cancer and renal disease.

An analysis of phenotypic and genetic variation including skin color and socio-economic status was carried out in the population of Cape Verde which has a well documented history of contact between Europeans and Africans. The studies showed that pattern of admixture in this population has been sex-biased and there is a significant interactions between socio economic status and skin color independent of the skin color and ancestry. Another study shows an increased risk of graft-versus-host disease complications after transplantation due to genetic variants in human leukocyte antigen (HLA) and non-HLA proteins.

Health

Differences in allele frequencies contribute to group differences in the incidence of some monogenic diseases, and they may contribute to differences in the incidence of some common diseases. For the monogenic diseases, the frequency of causative alleles usually correlates best with ancestry, whether familial (for example, Ellis-van Creveld syndrome among the Pennsylvania Amish), ethnic (Tay–Sachs disease among Ashkenazi Jewish populations), or geographical (hemoglobinopathies among people with ancestors who lived in malarial regions). To the extent that ancestry corresponds with racial or ethnic groups or subgroups, the incidence of monogenic diseases can differ between groups categorized by race or ethnicity, and health-care professionals typically take these patterns into account in making diagnoses.

Even with common diseases involving numerous genetic variants and environmental factors, investigators point to evidence suggesting the involvement of differentially distributed alleles with small to moderate effects. Frequently cited examples include hypertension (Douglas et al. 1996), diabetes (Gower et al. 2003), obesity (Fernandez et al. 2003), and prostate cancer (Platz et al. 2000). However, in none of these cases has allelic variation in a susceptibility gene been shown to account for a significant fraction of the difference in disease prevalence among groups, and the role of genetic factors in generating these differences remains uncertain (Mountain and Risch 2004).

Some other variations on the other hand are beneficial to human, as they prevent certain diseases and increase the chance to adapt to the environment. For example, mutation in CCR5 gene that protects against AIDS. CCR5 gene is absent on the surface of cell due to mutation. Without CCR5 gene on the surface, there is nothing for HIV viruses to grab on and bind into. Therefore, the mutation on CCR5 gene decreases the chance of an individual's risk with AIDS. The mutation in CCR5 is also quite common in certain areas, with more than 14% of the population carry the mutation in Europe and about 6–10% in Asia and North Africa.

HIV attachment

Apart from mutations, many genes that may have aided humans in ancient times plague humans today. For example, it is suspected that genes that allow humans to more efficiently process food are those that make people susceptible to obesity and diabetes today.

Neil Risch of Stanford University has proposed that self-identified race/ethnic group could be a valid means of categorization in the US for public health and policy considerations. A 2002 paper by Noah Rosenberg's group makes a similar claim: "The structure of human populations is relevant in various epidemiological contexts. As a result of variation in frequencies of both genetic and nongenetic risk factors, rates of disease and of such phenotypes as adverse drug response vary across populations. Further, information about a patient’s population of origin might provide health care practitioners with information about risk when direct causes of disease are unknown." However, in 2018 Noah Rosenberg released a study arguing against genetically essentialist ideas of health disparities between populations stating environmental variants are a more likely cause Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences

Genome projects

Human genome projects are scientific endeavors that determine or study the structure of the human genome. The Human Genome Project was a landmark genome project.

Removable partial denture

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Removable_partial_denture 

 

Removable partial denture
MeSH	D003832

A removable partial denture (RPD) is a denture for a partially edentulous patient who desires to have replacement teeth for functional or aesthetic reasons and who cannot have a bridge (a fixed partial denture) any reason, such as a lack of required teeth to serve as support for a bridge (i.e. distal abutments) or financial limitations.

This type of prosthesis is referred to as a removable partial denture because patients can remove and reinsert it when required without professional help. Conversely, a "fixed" prosthesis can and should be removed only by a dental professional.

Usage

RPD may be used when there is a lack of required teeth to serve as support for a bridge (i.e. distal abutments) or financial limitations. A single-tooth RPD known as a "flipper tooth" may be used temporarily after a tooth is extracted, during the several months it takes to complete the placement of a dental implant and crown.

Classification

The images above show the same Removable Partial Denture (RPD) for a patient whose mandible is partially edentulous. Their mouth is Kennedy classification II RPD as evidenced by the unilateral row of teeth on the right side of the denture. An embrasure clasp is viewable on the device's left half, as well as two cingulum rests for the two canine's on the mandible. The major connector is either a lingual bar or a sublingual bar.

The patient's oral condition is categorized based on the remaining dentition in a classification first proposed by Dr. Edward Kennedy in 1925. His classification consisted of four general outlines for partially edentulous arches that can present within a patient, which then could be treated with an RPD. When there is an edentulous space that is outside of the four classifications, it is termed a modification space. The use of this classification allows for easier communication between dental professionals, allows for easily visualization of the arch, and distinguishes a tooth-borne or tissue-supported RPD.

• Class I (bilateral free ended partially edentulous)
• Class II (unilateral free ended partially edentulous)
• Class III (unilateral bounded partially edentulous)
• Class IV (bilateral bounded anterior partially edentulous)

Kennedy Class I RPDs are fabricated for people who are missing some or all of their posterior teeth on both sides (left and right) in a single arch (either mandibular or maxillary), and there are no teeth posterior to the edentulous area. In other words, Class I RPDs clasp onto teeth that are more towards the front of the mouth, while replacing the missing posterior teeth on both sides with false denture teeth. The denture teeth are composed of either plastic or porcelain.

Class II RPDs are fabricated for people who are missing some or all of their posterior teeth on one side (left or right) in a single arch, and there are no teeth behind the edentulous area. Thus, Class II RPDs clasp onto teeth that are more towards the front of the mouth, as well as on teeth that are more towards the back of the mouth of the side on which teeth are not missing, while replacing the missing more-back-of-the-mouth teeth on one side with false denture teeth.

Class III RPDs are fabricated for people who are missing some teeth in such a way that the edentulous area has teeth remaining both posterior and anterior to it. Unlike Class I and Class II RPDs which are both tooth-and-tissue-borne (meaning they both clasp onto teeth, as well as rest on the posterior edentulous area for support), Class III RPDs are strictly tooth-borne, which means they only clasp onto teeth and do not need to rest on the tissue for added support. This makes Class III RPDs exceedingly more secure as per the three rules of removable prostheses that will be mentioned later, namely: support, stability and retention.

However, if the edentulous area described in the previous paragraph crosses the anterior midline (that is, at least both central incisors are missing), the RPD is classified as a Class IV RPD. By definition, a Kennedy Class IV RPD design will possess only one edentulous area.

Class I, II and III RPDs that have multiple edentulous areas in which replacement teeth are being placed are further classified with modification states that were defined by Oliver C. Applegate. Kennedy classification is governed by the most posterior edentulous area that is being restored. Thus if, for example, a maxillary arch is missing teeth #1, 3, 7-10 and 16, the RPD would be Kennedy Class III mod 1. It would not be Class I, because missing third molars are generally not restored in an RPD (although if they were, the classification would indeed be Class I), and it would not be Class IV, because modification spaces are not allowed for Kennedy Class IV.

The results of a study conducted in Saudi Arabia, showed that the occurrence of Kennedy Class III partial edentulism was 67.2% in the maxillary arch and 64.1% in the mandibular arch. Followed by Class II in both maxillary and mandibular arch with an average of 16.3% in maxillary arch and 14.8% in the mandibular arch. Based on these results, class III has the highest prevalence in younger group of patient (31– 40 years). Class I and class II have the highest incidence among older group of Patients (41–50 years).

Design

Prior to designing partial dentures a complete examination is undertaken to assess the condition of remaining teeth. This may involve radiographs, sensibility testing or other assessments. From this examination and assessment of occlusion (occlusal plane, drifting, tilting of teeth and surveyed articulated casts) the designing of partial dentures can begin. Information from previous dentures can be very useful in deciding which features to keep the same and which features of the design to change – in the hope of making an improvement.

Stages of partial denture design

A systematic design process should be followed:

• The teeth to be replaced must be decided.
• The soft tissue to be replaced (flange) is then drawn.
• The major connector is selected from a list of options (the options available will depend on the above assessment).
• Retentive features of the denture must be decided – these may include clasps, guide planes and indirect retention (often important in dentures involving Kennedy Class 1 and Class 2 saddles).
• Supportive features are then decided – these prevent the denture sinking into the soft tissue; often the natural teeth can take some of the loading (rest seats and connector coverage).

However, this is not always possible. Support may thus be tooth-borne, mucosal borne or a combination of tooth and mucosal borne.

• The denture should where possible have features that withstand horizontal movement (bracing) and the clasps should have appropriate reciprocation.
• The denture base material (usually acrylic or cobalt-chromium) and materials of the various components must be selected.
• The hygiene of the prosthesis must be appropriate trying where possible to minimise the soft tissues coverage.

The design should be reviewed and simplified removing unnecessary components.

Once the partial denture has been designed, the shade and mould of the replacement teeth can be selected. Within the design process (and prior to the master impression stage of denture construction), modifications may be suggested to teeth. This may be undertaken to create occlusal space for rest seats or to create undercuts for the placement of clasps (such as addition of composite resin) or to create guide planes for easier insertion and removal of the denture.

Components

Removable partial denture made from flexible nylon resin

Rather than lying entirely on the edentulous ridge like complete dentures, removable partial dentures possess clasps of cobalt-chrome or titanium metal or plastic that "clip" onto the remaining teeth, making the RPD more stable and retentive.

The parts of an RPD can be listed as follows (and are exemplified by the picture above):

• Major connector (The thick metal "U" in the RPD image above is a lingual bar, a type of major connector)
  • Anterior-posterior palatal strap
  • Single palatal strap
  • U-shaped palatal connector (Horseshoe)
  • Lingual bar
  • Lingual plate
• Minor connector (See the small struts protruding from the lingual bar at roughly 90 degree angles.)
• Direct retainer (Examples are in the upper left of upper photo and lower right of lower photo; the clasp arms act to hug the teeth and keep the RPD in place. The metal clasp and rest immediately adjacent to the denture teeth is also a direct retainer.)
• Indirect retainer (An example is the little metal piece coming off the "U" at a 90 degree angle near the top of the upper photo, which is a cingulum rest on a canine.)
  • Physical retainer (This is a mesh of metal that allows the pink base material to connect to the metal framework of the RPD. Some consider physical retainers their own component (making a total of seven), while others consider them within the indirect retainer category (thus making a total of six components.)
• Base (the pink material, mimicking gingiva)
• Teeth (plastic or porcelain formed in the shape of teeth)

Major connectors for upper teeth

Acrylic denture plate

 

Palatal bar

 

U shaped or "horse shoe" denture

 

Spoon denture

There are many options for major connectors for removable upper partial dentures. The type of connector used will vary depending on the specific circumstances and the results of a comprehensive examination and discussion with the patient. Commonly used major connectors are outlined in the table below along with details of factors affecting the choice of using them.

Plate

Advantages of plates are that they are useful when several teeth are missing or there are multiple saddle. They also provide more retention, stability and support due to larger palatal coverage. Plates are useful when there are long distal extensions.

Disadvantages of plates are that they overs a lot of patients mouth so sometimes not well tolerated and also may affect phonetics. Plates can be problematic if there is a torus palatinus.

Palatal bar (Strap/Anterior-Posterior)

Advantages of these are their rigidity and minimal soft tissue coverage yet still having good resistance to deformation. A-P strap useful for Kennedy class I and II or if there is a torus. A-P strap gives greater distribution of stresses.

Disadvantages of these are that there is not much support due to less palatal coverage and also that is it bulky and so disliked by some patients.

U-shaped palatal bar (horseshoe connector)

Advantages of these are that they are useful in cases where we do not want to cover much of the palate e.g. if patient has a strong gag reflex, a large palatal torus or Kennedy class III.

Disadvantages of these are that they are flexible due to distal extensions which can have adverse effects on force transmission to abutment teeth. They can traumatic to the residual ridge.

Spoon denture

Advantages of these are that they are useful in small anterior saddles and are cheap to make.

Disadvantages of these are that they have large palatal coverage for a small saddle.

Palatal Strap/Bar (Single/Anterior, mid or Posterior)

Advantages of these are that single strap is useful for Kennedy class III and IV cases.

Disadvantage of these are that single strap requires careful placement if there is a torus palatinus. They are generally inappropriate for Kennedy Class 1 or 2.

Major connectors for lower teeth

Lingual bar

 

Sublingual bar

 

Lingual plate

 

Buccal bar (Note the lingual tilting of the teeth meaning a buccal bar is required for a suitable path of insertion/removal.)

A major connector is the part of a partial denture that links components on one side of the arch with those on the other. It must be strong and rigid enough to provide a suitable skeleton to the prosthesis and located so as not to damage the gingival or movable tissues. Five types of major connectors are listed below:

Lingual bar

A lingual bar has a pear-shaped cross section tapering towards the gingival boundary. It should be positioned high enough so as to not irritate the lower movable tissue but low enough to allow for a substantial quantity of material to be used to ensure stiffness. At least 7mm of space is usually required. It sits on the soft tissue posteriorly to the dentition. Along with the lingual plate it is the most commonly used type of connector in the lower arch.

A lingual bar is more hygienic than a lingual plate but is difficult to add to if teeth are later extracted and require to be added to the denture.

Sublingual bar

A sublingual bar is similar to a lingual bar but is located on the floor of the mouth posteriorly and inferiorly to its usual location. They are used when the superior border of a lingual bar would be positioned too closely to the gingival border. They are contraindicated in patients with a high lingual frenum and in situations where they may interfere with tongue movements.

Lingual Plate

A lingual plate is a thin plate contoured to the lingual surfaces of the lower anterior teeth. A lingual plate is useful when there is insufficient space for a lingual bar which would result in irritation of the gingival boundary.

If the teeth are spaced out and the patient does not wish for visible metal to be seen then an interrupted lingual plate may be used where the material is cut away where it would be visible anteriorly.

A disadvantage of a lingual plate is that it covers a lot of gingival margins and is less hygienic than a lingual bar. It should be used with caution in those patients with a high caries rate. A major advantage is that is easier to add teeth to a denture with a lingual plate than a lingual bar connector. In addition, it is useful in providing some additional support for mobile lower anterior teeth.

Buccal bar

In rare cases where the inclination of the remaining anterior teeth is problematic and the use of a lingual connector inappropriate, a buccal bar can be considered.

Continuous clasp

Continuous Clasp in combination with a lingual bar

A continuous clasp is sometimes used in addition to a lingual bar and rarely as a sole major connector. It involves a bar of material placed along the cingulum of the anterior dentition.

The continuous clasp has the added advantage of providing indirect retention when used in addition to a lingual bar. It may be used when a lingual plate is compromising aesthetics.

Clasp design

Direct retainers may come in various designs:

• Cast circumferential clasp (suprabulge)
  • Akers'
  • Half and half
  • Back-action
  • Ring clasp
• Wrought wire clasp
• Roach clasp (infrabulge)
  • I-bar
  • T-bar
  • Y-bar
  • 7-bar

Both cast circumferential and wrought wire clasps are supra bulge clasps, in that they engage an undercut on the tooth by originating coronal to the height of contour, while Roach clasps are infrabulge clasps and engage undercuts by approaching from the gingival.

In addition there are a couple of specific theories which include the clasp design:

• RPI: mesial rest, distolingual guide plate, I-bar
  • The RPI design was made for clasping a bilateral free end extension. These clasps are unique because they have to take into account extra torque force due to being tissue borne (and not tooth borne) at the posterior.
  • Described by Kratochvil in 1963 and modified by Krol in 1973
    • Kratochvil designed the abutment tooth with a long rest (from the mesial marginal ridge to the distal pit), long guide plane, and a regular I-bar clasp.
    • Krol modified this design with a short occlusal rest, short guide plane (touching only from occlusal to middle third), and a mesial-shifted I-bar. The theory behind Krol's decision was to allow for movement of the partial denture without placing too much torque on the abutment tooth.
  • An illustration of the RPI design function
• RPA: mesial rest, distolingual guide plate, Akers' clasp-style retentive arm
• RPC: mesial rest, distolingual guide plate, other type of cast circumferential clasp
  • So named in response to the RPI Philosophy introduced by Kratochvil and Kroll

Indirect retention

Indirect retention is required to prevent displacement of saddles, such as free-end saddles or anterior saddle which is curved outside a straight line between the abutment teeth. Such indirect retention can only be achieved where both claps and rests work together to form lever system (Class III lever system) to retain the free part of denture.