founder effect

(genetics) The overrepresentation of a specific allele at one or more loci in a new population that arises from a small number of individuals whose small gene pool may be unrepresentative of the parental population initially or as a result of the ensuing genetic drift.

The term "founder effect" refers to the observation that when a small group of individuals breaks off from a larger population and establishes a new population, chance plays a large role in determining which alleles are represented in the new population. The particular alleles may not be representative of the larger population. As the new population grows, the allele frequencies will usually continue to reflect the original small group.

Genetic Characteristics of Founder Populations

Because the founder population is small, genetic drift can play an important role in determining the genetic makeup of subsequent generations, and allele frequencies may fluctuate. For example, consider an extreme situation where a new population is founded by just two individuals, a male and a female, perhaps because they are stranded on an island. Assume that the mother is heterozygous for a particular allele (Aa), while the father is homozygous (AA). If the couple has two children, there is a 25 percent chance that the mother will pass the A allele to both children.

If neither child inherits the allele, the a allele is effectively lost from the population. Even as they grow, many founder populations remain relatively genetically isolated, with little immigration into the population. Examples include founder populations that have remained isolated due to geographical location, such as Finland and Iceland, or due to religious customs, such as Amish and Hasidic Jewish groups.

Founder populations may have increased prevalence of certain genetic traits, including genetic disease. Disease alleles that happen to be present in the founders may be passed on to offspring, and, since the population is small, there may be a higher prevalence of the disease than in other, larger populations. Isolated founder populations, with little marriage outside of the populations, are especially likely to have a higher prevalence of recessive disorders, since parents are likely to share many genes, and there is an increased chance of inheriting two copies of a particular disease gene. Examples of rare genetic diseases that are prevalent in founder populations are Tay-Sachs disease in Ashkenazic Jewish populations and asthma in the Hutterian population.

Founder Populations Can Be Valuable for Genetic Studies

The same forces that lead to increased risk of disease also make founder populations particularly useful for identifying which genes are involved in genetic disease. Since the founder population is derived from a small number of individuals, it is likely that those individuals with a particular disease have a common genetic profile, rather than having multiple different disease mutations or susceptibility alleles. This genetic homogeneity is important, since genetic heterogeneity can make identification of any particular disease allele very difficult.

Linkage disequilibrium mapping is a powerful method for fine-mapping disease genes in founder populations. Linkage disequilibrium refers to the physical association between harmless but traceable marker alleles and a disease allele on a chromosome. The close proximity of the markers can help pinpoint the disease locus. Founder populations are particularly useful for linkage disequilibrium mapping since regions in linkage disequilibrium often span greater chromosomal distances than in general populations; that is, the disease gene will often be found with a larger set of common markers in a founder population than in a larger, more diverse population. This is expected because in founder populations, all chromosomes carrying a specific disease allele may be descended from a single ancestral chromosome, thus the disease allele will be in linkage disequilibrium with alleles at nearby markers. In a larger, more diverse population, the disease allele may have arisen on several different chromosomes, therefore the linkage disequilibrium, even for very close markers, may not be as great.

One example of linkage disequilibrium mapping in founder populations is the identification of a region containing the diastrophic dysplasia gene in eighteen families from Finland. This condition causes bent or abnormal bone growth. The region to which the disease gene was localized was narrowed substantially because scientists were able to take advantage of the extensive linkage disequilibrium around this gene in the affected individuals, all of whom shared a series of alleles surrounding the disease gene.

A related method for mapping disease genes that is well-suited for founder populations is haplotype analysis. A haplotype is defined as the set of alleles that are inherited as a group from one parent. A haplotype forms an identifiable pattern that can be used to track inheritance of all the genes within it. There are only a small number of haplotypes among the founders. Recombination tends to break up haplotypes over time, with the alleles that are closest together remaining together the longest.

A haplotype that is constantly inherited with a disease can be analyzed to narrow the region in which the gene should be sought. This means that researchers can look for shared regions or segments of chromosomes among affected individuals to help identify the location of a disease gene. For example, genetic researchers were able to demonstrate that the majority of cases of idiopathic torsion dystonia (a neurological disease) in Ashkenazic Jews were due to a single mutation from a common ancestor, because the affected individuals shared common alleles (a consistent haplotype) on either side of the mutation.

Another advantage of genetic studies in founder populations is that good clinical and genealogical recordkeeping is often available. Many genetic studies have been successful in Finland because of the population history of this region. For instance, the current Finnish population is believed to have come from a small group of individuals who settled in the southwest part of the country about 2,000 years ago. Since the initial immigration, the population has continued to be relatively isolated, with little migration into it.

Genealogical records are available through church parishes and often go back six to twelve generations, allowing scientists to develop accurate and detailed family histories linking individuals together. Despite these advantages, for common diseases such as asthma, scientists must consider that genes that cause asthma in Hutterites may or may not be relevant to other groups with asthma. Thus the scientist must weigh the advantages of performing genetic studies in small, historically isolated populations with the potential disadvantage of being unable to eventually generalize the studies' results.

Bibliography

Risch, Neil, et al. "Genetic Analysis of Idiopathic Torsion Dystonia in AshkenazicJews and Their Recent Descent from a Small Founder Population." Nature Genetics 9 (1995): 152-159.

Hastbacka, Johanna, et al. "Linkage Disequilibrium Mapping in Isolated FounderPopulations: Diastrophic Dysplasia in Finland." Nature Genetics 2, no. 3 (1992): 204-211.

Strachan, Tom, and Andrew P. Read. Human Molecular Genetics. New York: Wiley-Liss, 1996.

—Eden R. Martin and Marcy C. Speer

Extreme genetic drift that occurs when a new population is based on only a few individuals (‘founders’). Called also founder principle.

For the concept in organizations, see Founder's syndrome.

Simple illustration of founder effect. The original population is on the left with three possible founder populations on the right.

The founder effect was defined by Ernst Mayr in 1963 to be the effect of establishing a new population by a small number of individuals, carrying only a small fraction of the original population's genetic variation. As a result, the new population may be distinctively different, both genetically and phenotypically, from the parent population from which it is derived. In extreme cases, the founder effect is thought to lead to the speciation and subsequent evolution of new species. The founder effect is a feature that can also occur in memetic evolution.

In the figure shown, the original population has nearly equal numbers of blue and red individuals. The three smaller founder populations show that one or the other color may predominate (founder effect), due to random sampling of the original population. A population bottleneck may also cause a founder effect even though it is not strictly a new population.

In addition to founder effects, the new population is often a very small population and so shows increased sensitivity to genetic drift, an increase in inbreeding, and relatively low genetic variation. This can be observed in the limited gene pool of Easter Islanders and those native to Pitcairn Island.

Founder effects in island ecology

Founder populations are essential to the study of island biogeography and island ecology. A natural tabula rasa is not easily found, but a classic series of studies on founder population effects were done following the catastrophic 1883 eruption of Krakatau (Krakatoa), which erased all life on the island remnant. Another continuing study has been following the biocolonization of Surtsey, Iceland, a new volcanic island that erupted offshore between 1963 and 1967. An earlier event, the Toba eruption in Sumatra of about 73,000 YBP, covered some parts of India with 3–6 m of ash, and must have coated the Nicobar Islands and Andaman Islands, much nearer in the ash fallout cone, with life-smothering layers, restarting their biodiversity from effectively zero.

Founder effects in human populations

Due to various migrations throughout human history, founder effects are somewhat common among humans in different times and places. The effective founder population of Quebec was only 2,600. After twelve to sixteen generations, with an eighty-fold growth but minimal gene dilution from intermarriage, Quebec has what geneticists call optimal linkage disequilibrium (genetic sharing).^[1] The result: far fewer genetic variations, including those that have been well studied because they are connected with inheritable diseases.

Founder effects can also occur naturally as competing genetic lines die out. This means that an effective founder population consists only of those whose genetic print is identifiable in subsequent populations. Because in sexual reproduction, genetic recombination ensures that with each generation only half the genetic material of a parent is represented in the offspring, some genetic lines may die out entirely, even though there are numerous progeny. A recent study^[2] concluded that of the people migrating across the Bering land bridge at the close of the ice age, only 70 left their genetic print in modern descendants, a minute effective founder population— which is easily misread as though implying that only 70 people crossed to North America. The misinterpretations of "Mitochondrial Eve" are a case in point: it may be hard to explain that a "mitochondrial Eve" was not the only woman of her time.

In humans, founder effects can arise from cultural isolation, and inevitably, endogamy. For example, the Amish populations in the United States, which have grown from a very few founders, have not recruited newcomers, and tend to marry within the community, exhibit founder effects. Though still rare absolutely, phenomena such as polydactyly (extra fingers and toes, a symptom of Ellis-van Creveld syndrome) are more common in Amish communities than in the US population at large.^[3] Similar religious and cultural founder effects have been demonstrated through the prevalence of otherwise rare diseases among South African Muslims, among whom cleidocranial dysostosis is more common (due to one founder who was a Chinese immigrant who converted to Islam)^{[citation needed]}. There is also the presence of high cases of fumarase deficiency among the 10,000 members of the Fundamentalist Church of Jesus Christ of Latter Day Saints community, a breakaway sect which practices both endogamy and polygamy, where it is estimated 75 to 80 percent of the community are blood relatives of just two men - founders John Y. Barlow and Joseph Smith Jessop.^[4]

See also

• Small population size
• Last Common Ancestor

References

1. ^ genizon.com
2. ^ Hey, Jody, 2005. "On the Number of New World Founders: A Population Genetic Portrait of the Peopling of the Americas" in PLoS Biol 2005 May 24;3(6):e193 webpage
3. ^ McKusick, V. A.; Egeland, J. A.; Eldridge, R.; Krusen, D. E.: Dwarfism in the Amish. I. The Ellis-van Creveld syndrome. Bull. Johns Hopkins Hosp. 115: 306-336, 1964. PMID 14217223
4. ^ boston.com

• Mayr, E. 1963. Animal Species and Evolution. Harvard University Press, Cambridge, Massachusetts.

External links

• Founder effect
• Quebec Founder Population Project

Topics in population genetics
Key concepts	Hardy-Weinberg law • genetic linkage • linkage disequilibrium • Fisher's fundamental theorem • neutral theory
Selection	natural • sexual • artificial • ecological
Effects of selection on genomic variation	genetic hitchhiking • background selection
Genetic drift	small population size • population bottleneck • founder effect • coalescence
Founders	R.A. Fisher • J. B. S. Haldane • Sewall Wright
Related topics	evolution • microevolution • evolutionary game theory • fitness landscape • genetic genealogy
List of evolutionary biology topics

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