Founder Effect

In humans the founder result is divers every bit a decrease of genetic variation in the population due to a population bottleneck followed by random genetic drift.

From: Genomics of Rare Diseases , 2021

Genetic Variation in Populations

Robert 50. Nussbaum MD, FACP, FACMG , in Thompson & Thompson Genetics in Medicine , 2016

Founder Effect

Ane extreme example of a difference in the incidence of genetic disease among different ethnic groups is the high incidence ofHuntington disease ( Case 24 ) among the indigenous inhabitants around Lake Maracaibo, Venezuela, that resulted from the introduction of a Huntington disease mutation into this genetic isolate. There are numerous other examples of founder effect involving other disease alleles in genetic isolates throughout the world, such as the French-Canadian population of Canada, which has loftier frequencies of sure disorders that are rare elsewhere. For case, hereditary type I tyrosinemia is an autosomal recessive condition that causes hepatic failure and renal tubular dysfunction due to deficiency of fumarylacetoacetase, an enzyme in the degradative pathway of tyrosine. The disease frequency is ane in 685 in the Saguenay–Lac-Saint-Jean region of Quebec, only only ane in 100,000 in other populations. As predicted for a founder result, 100% of the mutant alleles in the Saguenay–Lac-Saint-Jean patients are due to the same mutation.

Thus one of the outcomes of the founder effect and genetic drift is that each population may be characterized by its own particular mutant alleles, also equally by an increase or decrease in specific diseases. The relative mobility of most present-solar day populations, in comparison with their ancestors of only a few generations agone, may reduce the outcome of genetic drift in the future while increasing the consequence of cistron flow.

Founder Consequence

T. Kivisild , in Brenner's Encyclopedia of Genetics (Second Edition), 2013

Abstract

Founder issue is the common upshot of the establishment of new populations from a small number of founding individuals. These founding individuals carry with them only a fraction of the genetic diversity of the parental population, and therefore, the founder effect results with a decreased genetic multifariousness and distinctive allele frequency patterns in the newly established population. The founder effect tin increase the frequency of certain rare disorders, while other disease alleles characteristic of the parental population may disappear. Disease alleles that accept negative upshot on fitness volition exist eliminated over fourth dimension, and somewhen, the signature of founder effect can exist erased.

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Human genetics

Jeannette Naish MBBS MSc FRCGP , in Medical Sciences , 2019

Founder effects

The founder effect was defined by Ernst Mayr as 'The institution of a new population by a few original founders (in an farthermost case, past a single fertilised female) which bear only a pocket-sized fraction of the total genetic variation of the parental population', and is recognised when a particular polymorphism can be traced dorsum to a single private.

The reasons for this phenomenon are twofold. Start, a particular surface area may go populated with a small-scale number of individuals, with all subsequent generations originating from these people while the particular population remains isolated ( Fig. 5.17 ) . For instance, many individuals living in Tristan da Cunha originate from the original British settlement of xv in 1816, one of whom was a carrier for retinitis pigmentosa, a disease which leads to premature blindness in affected homozygotes and has led to this disease remaining more prevalent in this small-scale island population than elsewhere.

The second reason concerns the origin of a detail set of Y chromosome polymorphisms. The male Y chromosome is passed without alter (other than rare mutations) through the generations. Thus, males with the same paternal ancestors are very likely to share identical Y chromosome polymorphism (known every bit ahaplotype, as there is only one Y chromosome).

Genghis Khan and the founder upshot

One particular Y chromosome haplotype is found in approximately 8% of the population in the old Mongolian Empire, and has spread throughout the world population. Although the success of this haplotype could be the result of it having some form of biological advantage, scientists have suggested that it could originate from the dynastic family unit of Genghis Khan and his male person relatives in their predominance and subsequent spread of the Mongolian Empire across the whole of Asia. Social norms were very different at the time and Khan'south male descendants appeared to have sired many sons from a high number of associations with women.

Genetic Colonization

J.B. Mitton , in Brenner'due south Encyclopedia of Genetics (2d Edition), 2013

Founder Upshot

The founder consequence is a paucity of genetic variation attributable to small constructive population size in a founding population. A small-scale number of individuals are non likely to comport a random sample of the genetic variation in a large, genetically diverse population, and then a small-scale group of individuals founding a population tin can be a unique subset of the variation in the large source population. The founder result could conceivably be a fortuitous sample, perhaps lacking deleterious, recessive alleles. But a common consequence is for founding populations to have higher levels of ane or a few deleterious alleles. For example, a founder effect during the institution of the Amish community in Pennsylvania, U.s., is credited for the elevated frequency of a syndrome characterized by dwarfism and polydactyly.

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Cerebellar Clutter

Joseph Jankovic Physician , in Bradley and Daroff's Neurology in Clinical Exercise , 2022

Regional and Ethnic Distributions of Spinocerebellar Clutter

SCAs ane, two, 3, 6, seven, and eight are virtually common in the United States and Europe, while geographic predilection of specific SCAs and distinctive founder effects exist in diverse parts of the globe ( Fig. 23.6). For example, a high prevalence has been institute for SCA1 in Poland; SCA2 in Cuba, Mexico, and Italy; SCA6 in UK, Germany, and Japan; SCA7 in South Africa, Mexico, and Venezuela; SCA10 in Latin America; SCA12 in India and Italy; while SCA3 is the most mutual SCA worldwide. Even so, only express population-based data (Coutinho et al., 2013) exist for incidence and prevalence of SCAs, and estimated frequency of SCAs in a given region is often reflecting founder effects.

The Evolution of Antibiotic Resistance

Fernando González-Candelas Iñaki Comas José Luis Martínez Juan Carlos Galán Fernando Baquero , in Genetics and Evolution of Communicable diseases, 2011

Glossary

Founder effect

the random alter in genetic composition of a population due to a extreme reduction in its size during a colonization or infection episode.

Genetic drift

the random alter in the genetic composition of a population due to its finite size. Every population experiences genetic drift but its effects, a reduction in genetic variation eventually leading to fixation of a variant, are more intense, both in magnitude and speed, the smaller its population size.

Mutator strains

bacterial strains with an increased mutation charge per unit ordinarily due to a defective mismatch-repair organization.

Pleiotropic animosity

the consequence of a gene on ii different traits with opposite consequences on fitness.

Resistome

the gear up of antibiotic-resistance genes or proteins found in a given environment.

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Recessive diseases and founder genetics

Erik G. Puffenberger , in Genomics of Rare Diseases, 2021

5.iii.3 Genomics of founder populations

Due to the founder event, many variants have drifted to allele frequencies that are significantly different from bachelor population controls. Therefore it is important to genetically study and sample individuals from these populations to create population-specific genomic databases that are informative for these populations. These databases are necessary to provide accurate population-specific allele frequencies for variants to enable appropriate filtering during analyses of genomic data for patients with rare diseases from these populations. Variants with frequencies that are besides high to be reasonably considered pathogenic can be more confidently excluded. Simultaneously, these databases enable the identification of salubrious control individuals who are homozygous for rare alleles in the population, deeming these variants unlikely to be pathogenic. This is specially true for founder populations where underlying levels of genome-broad homozygosity are loftier due to shared common ancestry, but besides for consanguineous populations that will take large genome-broad homozygous regions due to inbreeding. Furthermore, in cases of pathogenic variants, having a catalog of illness-associated variation in these populations enables rapid, early, and accurate diagnoses that may ameliorate patient outcomes due to informed clinical management and early interventions.

The explosion of population-level genomic data for founder and consanguineous populations has also highlighted new avenues for inquiry beyond disease gene identification. Owing to the presence of drifted alleles, founder populations have provided new insights into variant estimation and nomenclature which could non take been achieved previously. The presence of big numbers of heterozygotes for a globally rare allele affords the unusual ability to study the phenotypic impacts of these alleles at unprecedented resolution. For example, an allele in the KCNQ1 factor (c.671C>T, p.Thr224Met) was previously identified in two patients with long QT syndrome, but was however classified as a "variant of unknown significance (VUS)". The variant is extremely rare in the general population (1 heterozygote in 112,482 European control individuals), but relatively common in the Amish (1 in 45) [49]. The high prevalence of this allele immune researchers to identify 124 Amish heterozygotes and to perform detailed EKG studies on 88 carriers. The variant was shown to exist associated with a 20   ms longer QT interval than the normal allele. This information allowed the variant to exist reclassified as a "pathogenic" variant and led to culturally advisable return of results, including recommendations for treatment and cascade testing.

The pursuit to understand the function of each human gene has been most strongly avant-garde by the study of Mendelian diseases. The LoF of a gene in a diseased individual informs researchers about the normal role of that gene. A related and complementary method is to identify salubrious individuals who are homozygous for rare LoF alleles (so-called "human knockouts") and determine whether there is an associated phenotype with the natural absenteeism of that gene [44]. In these studies, founder populations, and peculiarly populations with a high level of consanguinity, have helped to elucidate the function of genes that contribute more than subtly to homo phenotypic variation [50]. It is particularly important to acknowledge that many of these phenotypic effects are actually medically beneficial, such as the finding of LoF variants in LPA in the Finnish population which confer protection against cardiovascular disease or the identification of a CCR5 homozygous LoF variant conferring resistance to HIV infection [51,52]. These studies enable a richer understanding of the genetic contribution to phenotypic variation in humans without relying solely on a classical disease model.

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Founder variations in isolated populations

Gabriela Chavarriá-Soley , ... Henriette Raventoś , in Genome Plasticity in Health and Affliction, 2020

ii Founder effects and linkage disequilibrium

In isolated populations, a founder effect can sometimes be involved in the loftier prevalence of certain disorders. The term founder effect, proposed past Mayr, xviii describes the establishment of a new population by a few original founders, which carries only a small fraction of the full genetic variation of the original population. For case, an allele for a Mendelian disorder can be very rare in the original population, but (by chance) exist present at a much higher frequency in the founder population. This can result in abnormally loftier frequencies of specific disorders in different population isolates after a few generations, often with additional activity of genetic migrate and inbreeding. This is the case of the Amish population of Lancaster County in Pennsylvania, which presents a loftier frequency of the autosomal recessive Ellis–van Creveld syndrome. 8

A founder effect in a population is suspected when there is an unusually loftier prevalence of some genetic disorder and/or a very low prevalence of others. When the subjects in the population are genotyped for i of these high prevalence disorders, if they share the same pathogenic variant as well equally surrounding genetic variants in a common haplotype, a founder mutation transmitted by a mutual ancestor is strongly suspected. one,19 The size of the shared haplotype identical by descent from the mutual ancestor will be inversely proportional to the number of generations to the founder (Fig. vi.one).

Figure 6.ane. Linkage disequilibrium around founder variants in isolated populations of unlike ages.

The iv colored horizontal confined correspond four bequeathed chromosomes. The star in the starting time bar represents a founder genetic variant. Ii hypothetical populations derived from a small number of founders are represented; a young isolate on the left and an former isolate on the right. The colored bars below represent the different haplotypes nowadays in each kind of isolate, with a reduction in the area in linkage disequilibrium evident for the older isolate.

The contribution of a founder effect for the detection of disease-associated genetic variants varies between Mendelian and complex disorders. 5,20 This is in part due to the different population frequencies of both kinds of disorders, and also to the different allele frequencies and effect sizes of risk variants involved. In Mendelian atmospheric condition, disease alleles are usually rare in the original population and information technology is probable that in a small number of founders a unmarried copy of an allele causing monogenic disease is nowadays. The consequence some generations after is that about all afflicted individuals will share the same illness-causing allele. For common complex disorders, both common and rare alleles play a role in the genetic architecture of illness. 21 Information technology is conceivable that a single re-create of a rare risk allele for a mutual disorder was present in a founding population and it tin can become common in the isolate because of genetic drift and/or inbreeding. Even so, detection of the adventure variant is affected by the effect size of the variant. Variants that increase risk by a very small amount are difficult to find. For common risk variants for common disorders, on the other manus, the founding population tin can have several different hazard alleles even if the size is small, and effect sizes of these alleles can potentially be very small—ii factors that complicate detection of risk variants. 22 Nonetheless, the argument tin can be made that even in such a case, the utilise of isolated populations tin exist benign for the study of complex disorders, because of a reduction of the background genetic multifariousness in the population. 1,23

When linkage disequilibrium (LD) is nowadays in a genomic region, some haplotypes (combinations of alleles along i chromosome) are institute more oftentimes than expected. In isolated populations, this reflects the allele combinations from the founders. As will be further discussed, the occurrence of high LD facilitates identification of genomic regions related to disease. Peculiarly in young isolates, the extension of LD can be much greater than in outbred populations. Older isolates have been found to prove comparable LD to outbred populations. 24

In genetic isolates, largely due to the beingness of founder effects and loftier LD, gene mapping can be performed at the population level instead of the family level. Platonic isolates for this purpose are those with a relatively low number of founders, followed by of import growth for 10–20 generations, and a current population large enough to discover several hundred individuals affected with the disorder of interest. 2

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FACIAL PARALANGUAGE AND GESTURE

ALAN J. FRIDLUND , in Human Facial Expression, 1994

Interpretation OF EVIDENCE FROM DIVERSE HUMAN POPULATIONS

It is tempting to effort to empathize the origins of the instances of paralanguage reported higher up, and to make up one's mind how much is conventional. Others have. Investigators like Birdwhistell and LaBarre used cultural differences in facial paralanguage to assert a cultural relativism and to mitigate a phyletic contribution. I consider this dispositiveness premature. As I have tried to make clear for nonparalinguistic facial displays, regional differences in facial paralanguage exercise not imply that it is conventional (i.e., epigenetic). Determination of what is "nature" and what is "nurture" in facial paralanguage is simply as labyrinthine, and whatsoever attempt must consider the post-obit:

1.

Genetic migrate or founder effects may have produced variations in facial paralanguage amongst diverse cultures. As I indicated in Chapter 11, these are strictly genetic mechanisms, simply they tin can produce quite pronounced variations in local populations that masquerade as "cultural."

2.

Population comparisons of facial paralanguage that detect regional variation must however control for language. Some paralanguage may be universally, innately coupled to certain aspects of language, but its manifestation would depend entirely upon the existence or nonexistence of those aspects of the linguistic communication in the given population. This signal can be clarified with an example. Conceivably, humans might be "prewired" to display a head tilt with eyebrow raise whenever they employ the subjunctive mood; the action might occur equally an illustrator during spoken language, or as an emblematic conversational response (symbolizing the sentence, "It could be true."). What if we found wide variations in usage of this display across geographic regions or cultures? It would be presumptuous to consider this a variation in display, because it might every bit well stand for a difference in linguistic communication. Populations that did non show the display might, for example, lack the subjunctive mood for demarcating counterfactuals (e.g., putatively the Chinese; run across Au, 1983; Bloom, 1981). Conversely, a population may lack the language for counterfactuals and depend upon paralanguage to denote them. And we simply practice not know what constitutes the innate, "deep structure" of facial paralanguage. It may be coupled with phonological, syntactic, and/or semantic features of language, and it may be "released" with the emphatic or prosodic features of particular dialects.

three.

Even if facial actions similar emblems appear wholly symbolic, information technology cannot exist assumed that they are only conventions. As I illustrated in the case of the hypothetical subjunctive-illustrator, and in my earlier discussion of display rules, rapid cultural development does not exclude phyletic contribution. To take a sample keepsake, Elvis Presley's cinematic sneer while speaking to female costars became a teenage American male amour display most instantaneously in the 1960s, although its use in contempt (and derision, scorn, etc.) was an excellent preadaptation. Are we to conclude that this emblem was entirely conventional (i.e., a learned token)? This position is defensible only if it is demonstrated that attitudes females found attractive in males did not change. Instead, the sneer may exist entirely canalized in displaying contempt, derision, and and then on, and Elvis Presley induced males tohave this attitude toward females. Ultimately, had the sneer persisted culturally, males genetically predisposed to sneering should have greater reproductive advantage. Furthermore, morphological change (a lip structure conducive to sneers) might get weakly selected for, just detecting such selection would take many generations.

four.

The above three dicta urge against the disqualification of a genetic basis for facial paralanguage even amongst population variations in it. Conversely, communalities in facial paralanguage among human being populations—or resemblances among human paralinguistic and nonhuman paravocal deportment—do not guarantee a phyletic contribution. This is so for the same arguments cited in my word of "facial expressions of emotion." Equally earlier, information technology is necessary to exclude cultural manual, convergent development, and common learning. Equally in those cases, both nonhuman and human ontogenetic data are crucial, even though the ideal human being experiments (i.e., blind children reared and taught to speak solely past blind caretakers) are wildly improbable and perchance ill advised.

These are but cautions. It is too early on to determine just which elements of facial paralanguage are under genetic control and which are conventional. Nosotros know far as well picayune about human facial paralanguage in even one population, much less across humanity in toto. And as I indicated with respect to putative "display rules," ethnographic and linguistic perspectives must come up to conduct before the beingness or nonexistence of any facial paralanguage is taken to implicate genetic versus epigenetic contributions.

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Speciation, Process of

Jeffrey 50. Feder , ... Peter J. Meyers , in Reference Module in Life Sciences, 2021

Genetic Drift

Although there is fence about whether drastic founder effects and population bottlenecks enable dramatic adaptive meridian shifts triggering speciation ( Templeton, 2008), this does not mean that genetic drift does non sometimes play an important role in population difference. As neutral or near neutral differences accumulate between populations in allopatry they may create large and numerous depressions of decreased fitness in the adaptive mural in hybrids due to B–D–G incompatibilities. This is because mutations that are neutral or virtually neutral within demes are not necessarily inconsequential and may cause pregnant postzygotic isolation between populations when mixed in hybrids. As a upshot, equally many slight differences accrue between allopatric populations, a highly convoluted and holey adaptive landscape tin exist for individuals of mixed ancestry, generating a high caste of RI and severely restricting gene menstruation genome wide between taxa (Gavrilets, 2004). In addition, during early stages of speciation with gene menstruation, the initial build upwards genetic divergence prior to a tipping point being reached and genomic hitchhiking being enabled may accept dynamics that are equivalent to genetic drift, as many selected sites may be just slightly favored and bear as if they are neutral until enough differences have accumulate to reduce the constructive migration rate between populations genome wide (Flaxman et al., 2013; Feder et al., 2014).

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