Enlightenment in Buddhism

From Wikipedia, the free encyclopedia

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

The English term enlightenment is the western translation of various Buddhist terms, most notably bodhi and vimutti. The abstract noun bodhi, (/ˈboʊdi/; Sanskrit: बोधि; Pali: bodhi), the knowledge or wisdom, or awakened intellect, of a Buddha. The verbal root budh- means "to awaken," and its literal meaning is closer to awakening. Although the term buddhi is also used in other Indian philosophies and traditions, its most common usage is in the context of Buddhism. vimukti is the freedom from or release of the fetters and hindrances.

The term "enlightenment" was popularised in the Western world through the 19th century translations of Max Müller. It has the western connotation of general insight into transcendental truth or reality. The term is also being used to translate several other Buddhist terms and concepts, which are used to denote (initial) insight (prajna (Sanskrit), wu (Chinese), kensho and satori (Japanese)); knowledge (vidya); the "blowing out" (Nirvana) of disturbing emotions and desires; and the attainment of supreme Buddhahood (samyak sam bodhi), as exemplified by Gautama Buddha.

What exactly constituted the Buddha's awakening is unknown. It may probably have involved the knowledge that liberation was attained by the combination of mindfulness and dhyāna, applied to the understanding of the arising and ceasing of craving. The relation between dhyana and insight is a core problem in the study of Buddhism, and is one of the fundamentals of Buddhist practice.

In the western world the concept of (spiritual) enlightenment has taken on a romantic meaning. It has become synonymous with self-realization and the true self and false self, being regarded as a substantial essence being covered over by social conditioning.

Etymology

Bodhi, Sanskrit बोधि, "awakening," "perfect knowledge," "perfect knowledge or wisdom (by which a man becomes a बुद्ध [Buddha] or जिन [jina, arahant; "victorious," "victor", the illuminated or enlightened intellect (of a Buddha or जिन)."

It is an abstract noun, formed from the verbal root *budh-, Sanskrit बुध, "to awaken, to know," "to wake, wake up, be awake," "to recover consciousness (after a swoon)," "to observe, heed, attend to."

It corresponds to the verbs bujjhati (Pāli) and bodhati, बोदति, "become or be aware of, perceive, learn, know, understand, awake" or budhyate (Sanskrit).

The feminine Sanskrit noun of *budh- is बुद्धि, buddhi, "prescience, intuition, perception, point of view."

Translation

Robert S. Cohen notes that the majority of English books on Buddhism use the term "enlightenment" to translate the term bodhi. The root budh, from which both bodhi and Buddha are derived, means "to wake up" or "to recover consciousness". Cohen notes that bodhi is not the result of an illumination, but of a path of realization, or coming to understanding. The term "enlightenment" is event-oriented, whereas the term "awakening" is process-oriented. The western use of the term "enlighten" has Christian roots, as in Calvin's "It is God alone who enlightens our minds to perceive his truths".

Early 19th century bodhi was translated as "intelligence". The term "enlighten" was first being used in 1835, in an English translation of a French article, while the first recorded use of the term 'enlightenment' is credited (by the Oxford English Dictionary) to the Journal of the Asiatic Society of Bengal (February, 1836). In 1857 The Times used the term "the Enlightened" for the Buddha in a short article, which was reprinted the following year by Max Müller. Thereafter, the use of the term subsided, but reappeared with the publication of Max Müller's Chips from a german Workshop, which included a reprint from the Times-article. The book was translated in 1969 into German, using the term "der Erleuchtete". Max Müller was an essentialist, who believed in a natural religion, and saw religion as an inherent capacity of human beings. "Enlightenment" was a means to capture natural religious truths, as distinguished from mere mythology.

By the mid-1870s it had become commonplace to call the Buddha "enlightened", and by the end of the 1880s the terms "enlightened" and "enlightenment" dominated the English literature.

Related terms

Insight

Bodhi

Bodhi (Sanskrit, Pāli), from the verbal root budd, "to awaken", "to understand", means literally "to have woken up and understood". According to Johannes Bronkhorst, Tillman Vetter, and K.R. Norman, bodhi was at first not specified. K.R. Norman:

It is not at all clear what gaining bodhi means. We are accustomed to the translation "enlightenment" for bodhi, but this is misleading ... It is not clear what the buddha was awakened to, or at what particular point the awakening came.

According to Norman, bodhi may basically have meant the knowledge that nibbana was attained, due to the practice of dhyana. Originally only "prajna" may have been mentioned, and Tillman Vetter even concludes that originally dhyana itself was deemed liberating, with the stilling of pleasure or pain in the fourth jhana, not the gaining of some perfect wisdom or insight. Gombrich also argues that the emphasis on insight is a later development.

In Theravada Buddhism, bodhi refers to the realisation of the four stages of enlightenment and becoming an Arahant. In Theravada Buddhism, bodhi is equal to supreme insight, and the realisation of the four noble truths, which leads to deliverance. According to Nyanatiloka,

(Through Bodhi) one awakens from the slumber or stupor (inflicted upon the mind) by the defilements (kilesa, q.v.) and comprehends the Four Noble Truths (sacca, q.v.).

This equation of bodhi with the four noble truths is a later development, in response to developments within Indian religious thought, where "liberating insight" was deemed essential for liberation. The four noble truths as the liberating insight of the Buddha eventually were superseded by Pratītyasamutpāda, the twelvefold chain of causation, and still later by anatta, the emptiness of the self.

In Mahayana Buddhism, bodhi is equal to prajna, insight into the Buddha-nature, sunyata and tathatā. This is equal to the realisation of the non-duality of absolute and relative.

Prajna

In Theravada Buddhism pannā (Pali) means "understanding", "wisdom", "insight". "Insight" is equivalent to vipassana', insight into the three marks of existence, namely anicca, dukkha and anatta. Insight leads to the four stages of enlightenment and Nirvana.

In Mahayana Buddhism Prajna (Sanskrit) means "insight" or "wisdom", and entails insight into sunyata. The attainment of this insight is often seen as the attainment of "enlightenment".

Wu

wu is the Chinese term for initial insight.

Kensho and satori

Kensho and Satori are Japanese terms used in Zen traditions. Kensho means "seeing into one's true nature." Ken means "seeing", sho means "nature", "essence", c.q Buddha-nature. Satori (Japanese) is often used interchangeably with kensho, but refers to the experience of kensho. The Rinzai tradition sees kensho as essential to the attainment of Buddhahood, but considers further practice essential to attain Buddhahood.

East-Asian (Chinese) Buddhism emphasizes insight into Buddha-nature. This term is derived from Indian tathagata-garbha thought, "the womb of the thus-gone" (the Buddha), the inherent potential of every sentient being to become a Buddha. This idea was integrated with the Yogacara-idea of the ālaya vijñāna, and further developed in Chinese Buddhism, which integrated Indian Buddhism with native Chinese thought. Buddha-nature came to mean both the potential of awakening and the whole of reality, a dynamic interpenetration of absolute and relative. In this awakening it is realized that observer and observed are not distinct entities, but mutually co-dependent.

Knowledge

The term vidhya is being used in contrast to avidhya, ignorance or the lack of knowledge, which binds us to samsara. The Mahasaccaka Sutta describes the three knowledges which the Buddha attained:

1. Insight into his past lives
2. Insight into the workings of Karma and Reincarnation
3. Insight into the Four Noble Truths

According to Bronkhorst, the first two knowledges are later additions, while insight into the four truths represents a later development, in response to concurring religious traditions, in which "liberating insight" came to be stressed over the practice of dhyana.

Freedom

Vimukthi, also called moksha, means "freedom", "release", "deliverance". Sometimes a distinction is being made between ceto-vimukthi, "liberation of the mind", and panna-vimukthi, "liberation by understanding". The Buddhist tradition recognises two kinds of ceto-vimukthi, one temporarily and one permanent, the last being equivalent to panna-vimukthi.

Yogacara uses the term āśraya parāvŗtti, "revolution of the basis",

... a sudden revulsion, turning, or re-turning of the ālaya vijñāna back into its original state of purity [...] the Mind returns to its original condition of non-attachment, non-discrimination and non-duality".

Nirvana

Nirvana is the "blowing out" of disturbing emotions, which is the same as liberation. The usage of the term "enlightenment" to translate "nirvana" was popularized in the 19th century, in part, due to the efforts of Max Muller, who used the term consistently in his translations.

Buddha's awakening

Buddhahood

Three types of buddha are recognized:

• Arhat (Pali: arahant), those who reach Nirvana by following the teachings of the Buddha. Sometimes the term Śrāvakabuddha (Pali: sāvakabuddha) is used to designate this kind of awakened person;
• Pratyekabuddhas (Pali: paccekabuddha), those who reach Nirvana through self-realisation, without the aid of spiritual guides and teachers, but don't teach the Dharma;
• Samyaksambuddha (Pali: samma sambuddha), often simply referred to as Buddha, one who has reached Nirvana by his own efforts and wisdom and teaches it skillfully to others.

Siddhartha Gautama, known as the Buddha, is said to have achieved full awakening, known as samyaksaṃbodhi (Sanskrit; Pāli: sammāsaṃbodhi), "perfect Buddhahood", or anuttarā-samyak-saṃbodhi, "highest perfect awakening". Specifically, anuttarā-samyak-saṃbodhi, literally meaning unsurpassed, complete and perfect enlightenment, is often used to distinguish the enlightenment of a Buddha from that of an Arhat.

The term Buddha has acquired somewhat different meanings in the various Buddhist traditions. An equivalent term for Buddha is Tathāgata, "the thus-gone". The way to Buddhahood is somewhat differently understood in the various Buddhist traditions.

The awakening of the Buddha

Canonical accounts

In the suttapitaka, the Buddhist canon as preserved in the Theravada tradition, a couple of texts can be found in which the Buddha's attainment of liberation forms part of the narrative.

The Ariyapariyesana Sutta (Majjhima Nikaya 26) describes how the Buddha was dissatisfied with the teachings of Alara Kalama and Uddaka Ramaputta, wandered further through Magadhan country, and then found "an agreeable piece of ground" which served for striving. The sutta then only says that he attained Nibbana.

In the Vanapattha Sutta (Majjhima Nikaya 17) the Buddha describes life in the jungle, and the attainment of awakening. The Mahasaccaka Sutta (Majjhima Nikaya 36) describes his ascetic practices, which he abandoned. Thereafter he remembered a spontaneous state of jhana, and set out for jhana-practice. Both suttas narrate how, after destroying the disturbances of the mind, and attaining concentration of the mind, he attained three knowledges (vidhya):

1. Insight into his past lives
2. Insight into the workings of Karma and Reincarnation
3. Insight into the Four Noble Truths

Insight into the Four Noble Truths is here called awakening. The monk (bhikkhu) has "...attained the unattained supreme security from bondage." Awakening is also described as synonymous with Nirvana, the extinction of the passions whereby suffering is ended and no more rebirths take place. The insight arises that this liberation is certain: "Knowledge arose in me, and insight: my freedom is certain, this is my last birth, now there is no rebirth."

Critical assessment

Schmithausen notes that the mention of the four noble truths as constituting "liberating insight", which is attained after mastering the Rupa Jhanas, is a later addition to texts such as Majjhima Nikaya 36. Bronkhorst notices that

...the accounts which include the Four Noble Truths had a completely different conception of the process of liberation than the one which includes the Four Dhyanas and the destruction of the intoxicants.

It calls in question the reliability of these accounts, and the relation between dhyana and insight, which is a core problem in the study of early Buddhism. Originally the term prajna may have been used, which came to be replaced by the four truths in those texts where "liberating insight" was preceded by the four jhanas. Bronkhorst also notices that the conception of what exactly this "liberating insight" was developed throughout time. Whereas originally it may not have been specified, later on the four truths served as such, to be superseded by pratityasamutpada, and still later, in the Hinayana schools, by the doctrine of the non-existence of a substantial self or person. And Schmithausen notices that still other descriptions of this "liberating insight" exist in the Buddhist canon:

"that the five Skandhas are impermanent, disagreeable, and neither the Self nor belonging to oneself"; "the contemplation of the arising and disappearance (udayabbaya) of the five Skandhas"; "the realisation of the Skandhas as empty (rittaka), vain (tucchaka) and without any pith or substance (asaraka).

An example of this substitution, and its consequences, is Majjhima Nikaya 36:42–43, which gives an account of the awakening of the Buddha.

Understanding of bodhi and Buddhahood

The term bodhi acquired a variety of meanings and connotations during the development of Buddhist thoughts in the various schools.

Early Buddhism

In early Buddhism, bodhi carried a meaning synonymous to nirvana, using only some different metaphors to describe the insight, which implied the extinction of lobha (greed), dosa (hate) and moha (delusion).

Theravada

In Theravada Buddhism, bodhi and nirvana carry the same meaning, that of being freed from greed, hate and delusion. In Theravada Buddhism, bodhi refers to the realisation of the four stages of enlightenment and becoming an Arahant. In Theravada Buddhism, bodhi is equal to supreme insight, the realisation of the four noble truths, which leads to deliverance. Reaching full awakening is equivalent in meaning to reaching Nirvāṇa. Attaining Nirvāṇa is the ultimate goal of Theravada and other śrāvaka traditions. It involves the abandonment of the ten fetters and the cessation of dukkha or suffering. Full awakening is reached in four stages. According to Nyanatiloka,

(Through Bodhi) one awakens from the slumber or stupor (inflicted upon the mind) by the defilements (kilesa, q.v.) and comprehends the Four Noble Truths (sacca, q.v.).

Since the 1980s, western Theravada-oriented teachers have started to question the primacy of insight. According to Thanissaro Bhikkhu, jhana and vipassana (insight) form an integrated practice. Polak and Arbel, following scholars like Vetter and Bronkhorst, argue that right effort, c.q. the four right efforts (sense restraint, preventing the arising of unwholesome states, and the generation of wholesome states), mindfulness, and dhyana form an integrated practice, in which dhyana is the actualisation of insight, leading to an awakened awareness which is "non-reactive and lucid."

Mahayana

In Mahayana-thought, bodhi is the realisation of the inseparability of samsara and nirvana, and the unity of subject and object. It is similar to prajna, to realizing the Buddha-nature, realizing sunyata and realizing suchness. In time, the Buddha's awakening came to be understood as an immediate full awakening and liberation, instead of the insight into and certainty about the way to follow to reach enlightenment. However, in some Zen traditions this perfection came to be relativized again; according to one contemporary Zen master, "Shakyamuni buddha and Bodhidharma are still practicing."

Mahayana discerns three forms of awakened beings:

1. Arahat – Liberation for oneself;
2. Bodhisattva – Liberation for living beings;
3. Full Buddhahood.

Within the various Mahayana-schools exist various further explanations and interpretations. In Mahāyāna Buddhism the Bodhisattva is the ideal. The ultimate goal is not only of one's own liberation in Buddhahood, but the liberation of all living beings. But Mahayana Buddhism also developed a cosmology with a wide range of buddhas and bodhisattvas, who assist humans on their way to liberation.

Nichiren Buddhism regards Buddhahood as a state of perfect freedom, in which one is awakened to the eternal and ultimate truth that is the reality of all things. This supreme state of life is characterized by boundless wisdom and infinite compassion. The Lotus Sutra reveals that Buddhahood is a potential in the lives of all beings.

Buddha-nature

In the Tathagatagarbha and Buddha-nature doctrines bodhi becomes equivalent to the universal, natural and pure state of the mind:

Bodhi is the final goal of a Bodhisattva's career [...] Bodhi is pure universal and immediate knowledge, which extends over all time, all universes, all beings and elements, conditioned and unconditioned. It is absolute and identical with Reality and thus it is Tathata. Bodhi is immaculate and non-conceptual, and it, being not an outer object, cannot be understood by discursive thought. It has neither beginning, nor middle nor end and it is indivisible. It is non-dual (advayam) [...] The only possible way to comprehend it is through samadhi by the yogin.

According to these doctrines bodhi is always there within one's mind, but requires the defilements to be removed. This vision is expounded in texts such as the Shurangama Sutra and the Uttaratantra.

In Shingon Buddhism, the state of Bodhi is also seen as naturally inherent in the mind. It is the mind's natural and pure state, where no distinction is being made between a perceiving subject and perceived objects. This is also the understanding of Bodhi found in Yogacara Buddhism.

To achieve this vision of non-duality, it is necessary to recognise one's own mind:

... it means that you are to know the inherent natural state of the mind by eliminating the split into a perceiving subject and perceived objects which normally occurs in the world and is wrongly thought to be real. This also corresponds to the Yogacara definition ... that emptiness (sunyata) is the absence of this imaginary split

Harmonisation of the various terms and meanings in Vajrayana Buddhism

During the development of Mahayana Buddhism the various strands of thought on Bodhi were continuously being elaborated. Attempts were made to harmonize the various terms. The Vajrayana Buddhist commentator Buddhaguhya treats various terms as synonyms:

For example, he defines emptiness (sunyata) as suchness (tathata) and says that suchness is the intrinsic nature (svabhava) of the mind which is Enlightenment (bodhi-citta). Moreover, he frequently uses the terms suchness (tathata) and Suchness-Awareness (tathata-jnana) interchangeably. But since Awareness (jnana) is non-dual, Suchness-Awareness is not so much the Awareness of Suchness, but the Awareness which is Suchness. In other words, the term Suchness-Awareness is functionally equivalent to Enlightenment. Finally, it must not be forgotten that this Suchness-Awareness or Perfect Enlightenment is Mahavairocana [the Primal Buddha, uncreated and forever existent]. In other words, the mind in its intrinsic nature is Mahavairocana, whom one "becomes" (or vice versa) when one is perfectly enlightened.

Western understanding of enlightenment

In the western world the concept of enlightenment has taken on a romantic meaning. It has become synonymous with self-realization and the true self, being regarded as a substantial essence being covered over by social conditioning.

Enlightenment as "Aufklärung"

The use of the western word enlightenment is based on the supposed resemblance of bodhi with Aufklärung, the independent use of reason to gain insight into the true nature of our world. In fact there are more resemblances with Romanticism than with the Enlightenment: the emphasis on feeling, on intuitive insight, on a true essence beyond the world of appearances.

Awakening

The equivalent term "awakening" has also been used in a Christian context, namely the Great Awakenings, several periods of religious revival in American religious history. Historians and theologians identify three or four waves of increased religious enthusiasm occurring between the early 18th century and the late 19th century. Each of these "Great Awakenings" was characterized by widespread revivals led by evangelical Protestant ministers, a sharp increase of interest in religion, a profound sense of conviction and redemption on the part of those affected, an increase in evangelical church membership, and the formation of new religious movements and denominations.

Romanticism and transcendentalism

The romantic idea of enlightenment as insight into a timeless, transcendent reality has been popularized especially by D.T. Suzuki. Further popularization was due to the writings of Heinrich Dumoulin. Dumoulin viewed metaphysics as the expression of a transcendent truth, which according to him was expressed by Mahayana Buddhism, but not by the pragmatic analysis of the oldest Buddhism, which emphasizes anatta. This romantic vision is also recognizable in the works of Ken Wilber.

In the oldest Buddhism this essentialism is not recognizable. According to critics it doesn't really contribute to a real insight into Buddhism:

...most of them labour under the old cliché that the goal of Buddhist psychological analysis is to reveal the hidden mysteries in the human mind and thereby facilitate the development of a transcendental state of consciousness beyond the reach of linguistic expression.

Enlightenment and experience

A common reference in western culture is the notion of "enlightenment experience". This notion can be traced back to William James, who used the term "religious experience" in his 1902 book, The Varieties of Religious Experience. Wayne Proudfoot traces the roots of the notion of "religious experience" further back to the German theologian Friedrich Schleiermacher (1768–1834), who argued that religion is based on a feeling of the infinite. Schleiermacher used the notion of "religious experience" to defend religion against the growing scientific and secular critique.

It was popularised by the Transcendentalists, and exported to Asia via missionaries. Transcendentalism developed as a reaction against 18th Century rationalism, John Locke's philosophy of Sensualism, and the predestination of New England Calvinism. It is fundamentally a variety of diverse sources such as Hindu texts like the Vedas, the Upanishads and the Bhagavad Gita, various religions, and German idealism.

It was adopted by many scholars of religion, of which William James was the most influential.

The notion of "experience" has been criticised. Robert Sharf points out that "experience" is a typical western term, which has found its way into Asian religiosity via western influences.

The notion of "experience" introduces a false notion of duality between "experiencer" and "experienced", whereas the essence of kensho is the realisation of the "non-duality" of observer and observed. "Pure experience" does not exist; all experience is mediated by intellectual and cognitive activity. The specific teachings and practices of a specific tradition may even determine what "experience" someone has, which means that this "experience" is not the proof of the teaching, but a result of the teaching. A pure consciousness without concepts, reached by "cleaning the doors of perception" as per romantic poet William Blake, would, according to Mohr, be an overwhelming chaos of sensory input without coherence.

Bodhi Day

Sakyamuni's awakening is celebrated on Bodhi Day. In Sri Lanka and Japan different days are used for this celebration. According to the Theravada tradition in Sri Lanka, Sakyamuni reached Buddhahood at the full moon in May. This is celebrated at Wesak Poya, the full moon in May, as Sambuddhatva jayanthi (also known as Sambuddha jayanthi). The Zen tradition claims the Buddha reached his decisive insight on 8 December. This is celebrated in Zen monasteries with a very intensive eight-day session of Rōhatsu.

Molecular evolution

From Wikipedia, the free encyclopedia

 

Evolutionary biology
Darwin's finches by John Gould

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

History

The history of molecular evolution starts in the early 20th century with comparative biochemistry, and the use of "fingerprinting" methods such as immune assays, gel electrophoresis and paper chromatography in the 1950s to explore homologous proteins. The field of molecular evolution came into its own in the 1960s and 1970s, following the rise of molecular biology. The advent of protein sequencing allowed molecular biologists to create phylogenies based on sequence comparison, and to use the differences between homologous sequences as a molecular clock to estimate the time since the last universal common ancestor. In the late 1960s, the neutral theory of molecular evolution provided a theoretical basis for the molecular clock, though both the clock and the neutral theory were controversial, since most evolutionary biologists held strongly to panselectionism, with natural selection as the only important cause of evolutionary change. After the 1970s, nucleic acid sequencing allowed molecular evolution to reach beyond proteins to highly conserved ribosomal RNA sequences, the foundation of a reconceptualization of the early history of life.

Forces in molecular evolution

The content and structure of a genome is the product of the molecular and population genetic forces which act upon that genome. Novel genetic variants will arise through mutation and will spread and be maintained in populations due to genetic drift or natural selection.

Mutation

This hedgehog has no pigmentation due to a mutation.

Mutations are permanent, transmissible changes to the genetic material (DNA or RNA) of a cell or virus. Mutations result from errors in DNA replication during cell division and by exposure to radiation, chemicals, and other environmental stressors, or viruses and transposable elements. Most mutations that occur are single nucleotide polymorphisms which modify single bases of the DNA sequence, resulting in point mutations. Other types of mutations modify larger segments of DNA and can cause duplications, insertions, deletions, inversions, and translocations.

Most organisms display a strong bias in the types of mutations that occur with strong influence in GC-content. Transitions (A ↔ G or C ↔ T) are more common than transversions (purine (adenine or guanine)) ↔ pyrimidine (cytosine or thymine, or in RNA, uracil)) and are less likely to alter amino acid sequences of proteins.

Mutations are stochastic and typically occur randomly across genes. Mutation rates for single nucleotide sites for most organisms are very low, roughly 10⁻⁹ to 10⁻⁸ per site per generation, though some viruses have higher mutation rates on the order of 10⁻⁶ per site per generation. Among these mutations, some will be neutral or beneficial and will remain in the genome unless lost via genetic drift, and others will be detrimental and will be eliminated from the genome by natural selection.

Because mutations are extremely rare, they accumulate very slowly across generations. While the number of mutations which appears in any single generation may vary, over very long time periods they will appear to accumulate at a regular pace. Using the mutation rate per generation and the number of nucleotide differences between two sequences, divergence times can be estimated effectively via the molecular clock.

Recombination

Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).

Recombination is a process that results in genetic exchange between chromosomes or chromosomal regions. Recombination counteracts physical linkage between adjacent genes, thereby reducing genetic hitchhiking. The resulting independent inheritance of genes results in more efficient selection, meaning that regions with higher recombination will harbor fewer detrimental mutations, more selectively favored variants, and fewer errors in replication and repair. Recombination can also generate particular types of mutations if chromosomes are misaligned.

Gene conversion

Gene conversion is a type of recombination that is the product of DNA repair where nucleotide damage is corrected using an homologous genomic region as a template. Damaged bases are first excised, the damaged strand is then aligned with an undamaged homolog, and DNA synthesis repairs the excised region using the undamaged strand as a guide. Gene conversion is often responsible for homogenizing sequences of duplicate genes over long time periods, reducing nucleotide divergence.

Genetic drift

Genetic drift is the change of allele frequencies from one generation to the next due to stochastic effects of random sampling in finite populations. Some existing variants have no effect on fitness and may increase or decrease in frequency simply due to chance. "Nearly neutral" variants whose selection coefficient is close to a threshold value of 1 / the effective population size will also be affected by chance as well as by selection and mutation. Many genomic features have been ascribed to accumulation of nearly neutral detrimental mutations as a result of small effective population sizes. With a smaller effective population size, a larger variety of mutations will behave as if they are neutral due to inefficiency of selection.

Selection

Selection occurs when organisms with greater fitness, i.e. greater ability to survive or reproduce, are favored in subsequent generations, thereby increasing the instance of underlying genetic variants in a population. Selection can be the product of natural selection, artificial selection, or sexual selection. Natural selection is any selective process that occurs due to the fitness of an organism to its environment. In contrast sexual selection is a product of mate choice and can favor the spread of genetic variants which act counter to natural selection but increase desirability to the opposite sex or increase mating success. Artificial selection, also known as selective breeding, is imposed by an outside entity, typically humans, in order to increase the frequency of desired traits.

The principles of population genetics apply similarly to all types of selection, though in fact each may produce distinct effects due to clustering of genes with different functions in different parts of the genome, or due to different properties of genes in particular functional classes. For instance, sexual selection could be more likely to affect molecular evolution of the sex chromosomes due to clustering of sex specific genes on the X, Y, Z or W.

Intragenomic conflict

Selection can operate at the gene level at the expense of organismal fitness, resulting in intragenomic conflict. This is because there can be a selective advantage for selfish genetic elements in spite of a host cost. Examples of such selfish elements include transposable elements, meiotic drivers, killer X chromosomes, selfish mitochondria, and self-propagating introns.

Genome architecture

Genome size

Genome size is influenced by the amount of repetitive DNA as well as number of genes in an organism. The C-value paradox refers to the lack of correlation between organism 'complexity' and genome size. Explanations for the so-called paradox are two-fold. First, repetitive genetic elements can comprise large portions of the genome for many organisms, thereby inflating DNA content of the haploid genome. Secondly, the number of genes is not necessarily indicative of the number of developmental stages or tissue types in an organism. An organism with few developmental stages or tissue types may have large numbers of genes that influence non-developmental phenotypes, inflating gene content relative to developmental gene families.

Neutral explanations for genome size suggest that when population sizes are small, many mutations become nearly neutral. Hence, in small populations repetitive content and other 'junk' DNA can accumulate without placing the organism at a competitive disadvantage. There is little evidence to suggest that genome size is under strong widespread selection in multicellular eukaryotes. Genome size, independent of gene content, correlates poorly with most physiological traits and many eukaryotes, including mammals, harbor very large amounts of repetitive DNA.

However, birds likely have experienced strong selection for reduced genome size, in response to changing energetic needs for flight. Birds, unlike humans, produce nucleated red blood cells, and larger nuclei lead to lower levels of oxygen transport. Bird metabolism is far higher than that of mammals, due largely to flight, and oxygen needs are high. Hence, most birds have small, compact genomes with few repetitive elements. Indirect evidence suggests that non-avian theropod dinosaur ancestors of modern birds ^[6] also had reduced genome sizes, consistent with endothermy and high energetic needs for running speed. Many bacteria have also experienced selection for small genome size, as time of replication and energy consumption are so tightly correlated with fitness.

Repetitive elements

Transposable elements are self-replicating, selfish genetic elements which are capable of proliferating within host genomes. Many transposable elements are related to viruses, and share several proteins in common.

Chromosome number and organization

The number of chromosomes in an organism's genome also does not necessarily correlate with the amount of DNA in its genome. The ant Myrmecia pilosula has only a single pair of chromosomes whereas the Adders-tongue fern Ophioglossum reticulatum has up to 1260 chromosomes. Cilliate genomes house each gene in individual chromosomes, resulting in a genome which is not physically linked. Reduced linkage through creation of additional chromosomes should effectively increase the efficiency of selection.

Changes in chromosome number can play a key role in speciation, as differing chromosome numbers can serve as a barrier to reproduction in hybrids. Human chromosome 2 was created from a fusion of two chimpanzee chromosomes and still contains central telomeres as well as a vestigial second centromere. Polyploidy, especially allopolyploidy, which occurs often in plants, can also result in reproductive incompatibilities with parental species. Agrodiatus blue butterflies have diverse chromosome numbers ranging from n=10 to n=134 and additionally have one of the highest rates of speciation identified to date.

Gene content and distribution

Different organisms house different numbers of genes within their genomes as well as different patterns in the distribution of genes throughout the genome. Some organisms, such as most bacteria, Drosophila, and Arabidopsis have particularly compact genomes with little repetitive content or non-coding DNA. Other organisms, like mammals or maize, have large amounts of repetitive DNA, long introns, and substantial spacing between different genes. The content and distribution of genes within the genome can influence the rate at which certain types of mutations occur and can influence the subsequent evolution of different species. Genes with longer introns are more likely to recombine due to increased physical distance over the coding sequence. As such, long introns may facilitate ectopic recombination, and result in higher rates of new gene formation.

Organelles

In addition to the nuclear genome, endosymbiont organelles contain their own genetic material typically as circular plasmids. Mitochondrial and chloroplast DNA varies across taxa, but membrane-bound proteins, especially electron transport chain constituents are most often encoded in the organelle. Chloroplasts and mitochondria are maternally inherited in most species, as the organelles must pass through the egg. In a rare departure, some species of mussels are known to inherit mitochondria from father to son.

Origins of new genes

New genes arise from several different genetic mechanisms including gene duplication, de novo origination, retrotransposition, chimeric gene formation, recruitment of non-coding sequence, and gene truncation.

Gene duplication initially leads to redundancy. However, duplicated gene sequences can mutate to develop new functions or specialize so that the new gene performs a subset of the original ancestral functions. In addition to duplicating whole genes, sometimes only a domain or part of a protein is duplicated so that the resulting gene is an elongated version of the parental gene.

Retrotransposition creates new genes by copying mRNA to DNA and inserting it into the genome. Retrogenes often insert into new genomic locations, and often develop new expression patterns and functions.

Chimeric genes form when duplication, deletion, or incomplete retrotransposition combine portions of two different coding sequences to produce a novel gene sequence. Chimeras often cause regulatory changes and can shuffle protein domains to produce novel adaptive functions.

De novo gene birth can also give rise to new genes from previously non-coding DNA. For instance, Levine and colleagues reported the origin of five new genes in the D. melanogaster genome from noncoding DNA. Similar de novo origin of genes has been also shown in other organisms such as yeast, rice and humans. De novo genes may evolve from transcripts that are already expressed at low levels. Mutation of a stop codon to a regular codon or a frameshift may cause an extended protein that includes a previously non-coding sequence. The formation of novel genes from scratch typically can not occur within genomic regions of high gene density. The essential events for de novo formation of genes is recombination/mutation which includes insertions, deletions, and inversions. These events are tolerated if the consequence of these genetic events does not interfere in cellular activities. Most genomes comprise prophages wherein genetic modifications do not, in general, affect the host genome propagation. Hence, there is higher probability of genetic modifications, in regions such as prophages, which is proportional to the probability of de novo formation of genes.

De novo evolution of genes can also be simulated in the laboratory. For example, semi-random gene sequences can be selected for specific functions. More specifically, they selected sequences from a library that could complement a gene deletion in E. coli. The deleted gene encodes ferric enterobactin esterase (Fes), which releases iron from an iron chelator, enterobactin. While Fes is a 400 amino acid protein, the newly selected gene was only 100 amino acids in length and unrelated in sequence to Fes.

In vitro molecular evolution experiments

Principles of molecular evolution have also been discovered, and others elucidated and tested using experimentation involving amplification, variation and selection of rapidly proliferating and genetically varying molecular species outside cells. Since the pioneering work of Sol Spiegelmann in 1967 [ref], involving RNA that replicates itself with the aid of an enzyme extracted from the Qß virus [ref], several groups (such as Kramers [ref] and Biebricher/Luce/Eigen [ref]) studied mini and micro variants of this RNA in the 1970s and 1980s that replicate on the timescale of seconds to a minute, allowing hundreds of generations with large population sizes (e.g. 10^14 sequences) to be followed in a single day of experimentation. The chemical kinetic elucidation of the detailed mechanism of replication [ref, ref] meant that this type of system was the first molecular evolution system that could be fully characterised on the basis of physical chemical kinetics, later allowing the first models of the genotype to phenotype map based on sequence dependent RNA folding and refolding to be produced [ref, ref]. Subject to maintaining the function of the multicomponent Qß enzyme, chemical conditions could be varied significantly, in order to study the influence of changing environments and selection pressures [ref]. Experiments with in vitro RNA quasi species included the characterisation of the error threshold for information in molecular evolution [ref], the discovery of de novo evolution [ref] leading to diverse replicating RNA species and the discovery of spatial travelling waves as ideal molecular evolution reactors [ref, ref]. Later experiments employed novel combinations of enzymes to elucidate novel aspects of interacting molecular evolution involving population dependent fitness, including work with artificially designed molecular predator prey and cooperative systems of multiple RNA and DNA [ref, ref]. Special evolution reactors were designed for these studies, starting with serial transfer machines, flow reactors such as cell-stat machines, capillary reactors, and microreactors including line flow reactors and gel slice reactors. These studies were accompanied by theoretical developments and simulations involving RNA folding and replication kinetics that elucidated the importance of the correlation structure between distance in sequence space and fitness changes [ref], including the role of neutral networks and structural ensembles in evolutionary optimisation.

Molecular phylogenetics

Molecular systematics is the product of the traditional fields of systematics and molecular genetics. It uses DNA, RNA, or protein sequences to resolve questions in systematics, i.e. about their correct scientific classification or taxonomy from the point of view of evolutionary biology.

Molecular systematics has been made possible by the availability of techniques for DNA sequencing, which allow the determination of the exact sequence of nucleotides or bases in either DNA or RNA. At present it is still a long and expensive process to sequence the entire genome of an organism, and this has been done for only a few species. However, it is quite feasible to determine the sequence of a defined area of a particular chromosome. Typical molecular systematic analyses require the sequencing of around 1000 base pairs.

The driving forces of evolution

Depending on the relative importance assigned to the various forces of evolution, three perspectives provide evolutionary explanations for molecular evolution.

Selectionist hypotheses argue that selection is the driving force of molecular evolution. While acknowledging that many mutations are neutral, selectionists attribute changes in the frequencies of neutral alleles to linkage disequilibrium with other loci that are under selection, rather than to random genetic drift. Biases in codon usage are usually explained with reference to the ability of even weak selection to shape molecular evolution.

Neutralist hypotheses emphasize the importance of mutation, purifying selection, and random genetic drift. The introduction of the neutral theory by Kimura, quickly followed by King and Jukes' own findings, led to a fierce debate about the relevance of neodarwinism at the molecular level. The Neutral theory of molecular evolution proposes that most mutations in DNA are at locations not important to function or fitness. These neutral changes drift towards fixation within a population. Positive changes will be very rare, and so will not greatly contribute to DNA polymorphisms. Deleterious mutations do not contribute much to DNA diversity because they negatively affect fitness and so are removed from the gene pool before long. This theory provides a framework for the molecular clock. The fate of neutral mutations are governed by genetic drift, and contribute to both nucleotide polymorphism and fixed differences between species.

In the strictest sense, the neutral theory is not accurate. Subtle changes in DNA very often have effects, but sometimes these effects are too small for natural selection to act on. Even synonymous mutations are not necessarily neutral because there is not a uniform amount of each codon. The nearly neutral theory expanded the neutralist perspective, suggesting that several mutations are nearly neutral, which means both random drift and natural selection is relevant to their dynamics. The main difference between the neutral theory and nearly neutral theory is that the latter focuses on weak selection, not strictly neutral.

Mutationists hypotheses emphasize random drift and biases in mutation patterns. Sueoka was the first to propose a modern mutationist view. He proposed that the variation in GC content was not the result of positive selection, but a consequence of the GC mutational pressure.

Protein evolution

This chart compares the sequence identity of different lipase proteins throughout the human body. It demonstrates how proteins evolve, keeping some regions conserved while others change dramatically.

Evolution of proteins is studied by comparing the sequences and structures of proteins from many organisms representing distinct evolutionary clades. If the sequences/structures of two proteins are similar indicating that the proteins diverged from a common origin, these proteins are called homologous proteins. More specifically, homologous proteins that exist in two distinct species are called orthologs. Whereas, homologous proteins encoded by the genome of a single species are called paralogs.

The phylogenetic relationships of proteins are examined by multiple sequence comparisons. Phylogenetic trees of proteins can be established by the comparison of sequence identities among proteins. Such phylogenetic trees have established that the sequence similarities among proteins reflect closely the evolutionary relationships among organisms.

Protein evolution describes the changes over time in protein shape, function, and composition. Through quantitative analysis and experimentation, scientists have strived to understand the rate and causes of protein evolution. Using the amino acid sequences of hemoglobin and cytochrome c from multiple species, scientists were able to derive estimations of protein evolution rates. What they found was that the rates were not the same among proteins. Each protein has its own rate, and that rate is constant across phylogenies (i.e., hemoglobin does not evolve at the same rate as cytochrome c, but hemoglobins from humans, mice, etc. do have comparable rates of evolution.). Not all regions within a protein mutate at the same rate; functionally important areas mutate more slowly and amino acid substitutions involving similar amino acids occurs more often than dissimilar substitutions. Overall, the level of polymorphisms in proteins seems to be fairly constant. Several species (including humans, fruit flies, and mice) have similar levels of protein polymorphism.

In his Dublin 1943 lectures, “What Is Life?”, Erwin Schrodinger proposed that we could progress in answering this question by using statistical mechanics and partition functions, but not quantum mechanics and his wave equation. He described an “aperiodic crystal” which could carry genetic information, a description credited by Francis Crick and James D. Watson with having inspired their discovery of the double helical structure of DNA. Twenty fractals were discovered in solvent associated surface areas of > 5000 protein segments. The existence of these fractals proves that proteins function near critical points of second-order phase transitions, realizing Schrodinger's conjecture. It opens a new biophysics field of accurate thermodynamic analysis of protein evolution based primarily on amino acid sequences 

Relation to nucleic acid evolution

Protein evolution is inescapably tied to changes and selection of DNA polymorphisms and mutations because protein sequences change in response to alterations in the DNA sequence. Amino acid sequences and nucleic acid sequences do not mutate at the same rate. Due to the degenerate nature of DNA, bases can change without affecting the amino acid sequence. For example, there are six codons that code for leucine. Thus, despite the difference in mutation rates, it is essential to incorporate nucleic acid evolution into the discussion of protein evolution. At the end of the 1960s, two groups of scientists—Kimura (1968) and King and Jukes (1969)—independently proposed that a majority of the evolutionary changes observed in proteins were neutral. Since then, the neutral theory has been expanded upon and debated.

Discordance with morphological evolution

There are sometimes discordances between molecular and morphological evolution, which are reflected in molecular and morphological systematic studies, especially of bacteria, archaea and eukaryotic microbes. These discordances can be categorized as two types: (i) one morphology, multiple lineages (e.g. morphological convergence, cryptic species) and (ii) one lineage, multiple morphologies (e.g. phenotypic plasticity, multiple life-cycle stages). Neutral evolution possibly could explain the incongruences in some cases.

Journals and societies

The Society for Molecular Biology and Evolution publishes the journals "Molecular Biology and Evolution" and "Genome Biology and Evolution" and holds an annual international meeting. Other journals dedicated to molecular evolution include Journal of Molecular Evolution and Molecular Phylogenetics and Evolution. Research in molecular evolution is also published in journals of genetics, molecular biology, genomics, systematics, and evolutionary biology.

Genetic disorder

From Wikipedia, the free encyclopedia

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

Genetic disorder
A boy with Down syndrome, one of the most common genetic disorders
Specialty	Medical genetics

A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development (a de novo mutation), or it can be inherited from two parents who are carriers of a faulty gene (autosomal recessive inheritance) or from a parent with the disorder (autosomal dominant inheritance). When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.

There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. More than 600 of these disorders are treatable. Around 1 in 50 people are affected by a known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder. Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to the significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as "rare" (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves.

All genetic disorders are present before birth, and some genetic disorders produce birth defects, but many birth defects are developmental rather than hereditary. The opposite of a hereditary disease is an acquired disease. Most cancers, although they involve genetic mutations to a small proportion of cells in the body, are acquired diseases. Some family cancer syndromes, such as BRCA mutations, are hereditary genetic disorders.

Diagram featuring examples of a disease located on each chromosome

Single-gene

Prevalence of some single-gene disorders

Disorder prevalence (approximate)
Autosomal dominant
Familial hypercholesterolemia	1 in 500
Polycystic kidney disease	1 in 750
Neurofibromatosis type I	1 in 2,500
Hereditary spherocytosis	1 in 5,000
Marfan syndrome	1 in 4,000
Huntington's disease	1 in 15,000
Autosomal recessive
Sickle cell anaemia	1 in 625
Cystic fibrosis	1 in 2,000
Tay–Sachs disease	1 in 3,000
Phenylketonuria	1 in 12,000
Mucopolysaccharidoses	1 in 25,000
Lysosomal acid lipase deficiency	1 in 40,000
Glycogen storage diseases	1 in 50,000
Galactosemia	1 in 57,000
X-linked
Duchenne muscular dystrophy	1 in 5,000
Hemophilia	1 in 10,000
Values are for liveborn infants

A single-gene disorder (or monogenic disorder) is the result of a single mutated gene. Single-gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy, however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although the divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, the common form of dwarfism, achondroplasia, is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe and usually lethal skeletal disorder, one that achondroplasics could be considered carriers for. Sickle-cell anemia is also considered a recessive condition, but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as a related dominant condition. When a couple where one partner or both are sufferers or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether the embryo has the genetic disorder.

Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects. Many such single-gene defects can decrease the fitness of affected people and are therefore present in the population in lower frequencies compared to what would be expected based on simple probabilistic calculations.

Autosomal dominant

Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance, which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease, neurofibromatosis type 1, neurofibromatosis type 2, Marfan syndrome, hereditary nonpolyposis colorectal cancer, hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), tuberous sclerosis, Von Willebrand disease, and acute intermittent porphyria. Birth defects are also called congenital anomalies.

Autosomal recessive

Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene and are referred to as genetic carriers. Each parent with a defective gene normally do not have symptoms. Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having a child affected by the disorder. Examples of this type of disorder are albinism, medium-chain acyl-CoA dehydrogenase deficiency, cystic fibrosis, sickle cell disease, Tay–Sachs disease, Niemann–Pick disease, spinal muscular atrophy, and Roberts syndrome. Certain other phenotypes, such as wet versus dry earwax, are also determined in an autosomal recessive fashion. Some autosomal recessive disorders are common because, in the past, carrying one of the faulty genes led to a slight protection against an infectious disease or toxin such as tuberculosis or malaria. Such disorders include cystic fibrosis, sickle cell disease, phenylketonuria and thalassaemia.

X-linked dominant

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets. Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, such as Rett syndrome, incontinentia pigmenti type 2, and Aicardi syndrome, are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (44+xxy) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), but his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected fetus with each pregnancy, although in cases such as incontinentia pigmenti, only female offspring are generally viable.

X-linked recessive

X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are much more frequently affected than females, because they only have the one X chromosome necessary for the condition to present. The chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected (since they receive their father's Y chromosome), but his daughters will be carriers of one copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (X^RX^r) has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers of one copy of the mutated gene. X-linked recessive conditions include the serious diseases hemophilia A, Duchenne muscular dystrophy, and Lesch–Nyhan syndrome, as well as common and less serious conditions such as male pattern baldness and red–green color blindness. X-linked recessive conditions can sometimes manifest in females due to skewed X-inactivation or monosomy X (Turner syndrome).

Y-linked

Y-linked disorders are caused by mutations on the Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected because they do not possess Y-allosomes.

Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions is only possible through the circumvention of infertility by medical intervention.

Mitochondrial

This type of inheritance, also known as maternal inheritance, is the rarest and applies to the 13 genes encoded by mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only mothers (who are affected) can pass on mitochondrial DNA conditions to their children. An example of this type of disorder is Leber's hereditary optic neuropathy.

It is important to stress that the vast majority of mitochondrial diseases (particularly when symptoms develop in early life) are actually caused by a nuclear gene defect, as the mitochondria are mostly developed by non-mitochondrial DNA. These diseases most often follow autosomal recessive inheritance.

Multifactorial disorder

Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person's risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. Studies that aim to identify the cause of complex disorders can use several methodological approaches to determine genotype–phenotype associations. One method, the genotype-first approach, starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity, penetrance, and expressivity.

On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. This does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure). Other factors include:

• asthma
• autoimmune diseases such as multiple sclerosis
• cancers
• ciliopathies
• cleft palate
• diabetes
• heart disease
• hypertension
• inflammatory bowel disease
• intellectual disability
• mood disorder
• obesity
• refractive error
• infertility

Chromosomal disorder

Chromosomes in Down syndrome, the most common human condition due to aneuploidy. There are three chromosomes 21 (in the last row).

A chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. It can be from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. An example of these disorders is trisomy 21 (Down syndrome), in which there is an extra copy of chromosome 21.

Diagnosis

Due to the wide range of genetic disorders that are known, diagnosis is widely varied and dependent of the disorder. Most genetic disorders are diagnosed pre-birth, at birth, or during early childhood however some, such as Huntington's disease, can escape detection until the patient is well into adulthood.

The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Prognosis

Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome, while others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington's disease, show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

Treatment

From personal genomics to gene therapy

The treatment of genetic disorders is an ongoing battle, with over 1,800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating the symptoms of the disorders in an attempt to improve patient quality of life.

Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of the disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. Researchers have investigated how they can introduce a gene into the potentially trillions of cells which carry the defective copy. Finding an answer to this has been a roadblock between understanding the genetic disorder and correcting the genetic disorder.

Epidemiology

Around 1 in 50 people are affected by a known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder. Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to the significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as "rare" (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves. There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature.

History

The earliest known genetic condition in a hominid was in the fossil species Paranthropus robustus, with over a third of individuals displaying amelogenesis imperfecta.

Locus (genetics)

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Locus_(genetics) 

 

Parts of a typical chromosome:

(1) Chromatid
(2) Centromere
(3) Short (p) arm
(4) Long (q) arm

In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total number of protein-coding genes in a complete haploid set of 23 chromosomes is estimated at 19,000–20,000.

Genes may possess multiple variants known as alleles, and an allele may also be said to reside at a particular locus. Diploid and polyploid cells whose chromosomes have the same allele at a given locus are called homozygous with respect to that locus, while those that have different alleles at a given locus are called heterozygous. The ordered list of loci known for a particular genome is called a gene map. Gene mapping is the process of determining the specific locus or loci responsible for producing a particular phenotype or biological trait.

Nomenclature

Cytogenetic banding nomenclature

The shorter arm of a chromosome is termed the p arm or p-arm, while the longer arm is the q arm or q-arm. The chromosomal locus of a typical gene, for example, might be written 3p22.1, where:

• 3 = chromosome 3
• p = p-arm
• 22 = region 2, band 2 (read as "two, two", not "twenty-two")
• 1 = sub-band 1

Thus the entire locus of the example above would be read as "three P two two point one". The cytogenetic bands are areas of the chromosome either rich in actively-transcribed DNA (euchromatin) or packaged DNA (heterochromatin). They appear differently upon staining (for example, euchromatin appears white and heterochromatin appears black on Giemsa staining). They are counted from the centromere out toward the telomeres.

Example of cytogenetic bands

Component	Explanation
3	The chromosome number
p	The position is on the chromosome's short arm (a common apocryphal explanation is that the p stands for petit in French); q indicates the long arm (chosen as next letter in alphabet after p; it is also said that q stands for queue, meaning "tail" in French).
22.1	The numbers that follow the letter represent the position on the arm: region 2, band 2, sub-band 1. The bands are visible under a microscope when the chromosome is suitably stained. Each of the bands is numbered, beginning with 1 for the band nearest the centromere. Sub-bands and sub-sub-bands are visible at higher resolution.

A range of loci is specified in a similar way. For example, the locus of gene OCA1 may be written "11q1.4-q2.1", meaning it is on the long arm of chromosome 11, somewhere in the range from sub-band 4 of region 1 to sub-band 1 of region 2.

The ends of a chromosome are labeled "pter" and "qter", and so "2qter" refers to the terminus of the long arm of chromosome 2.