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.
Eden R. Martin
and Marcy C. Speer
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.
In the nineteenth century, the rate of deafness on Martha's Vineyard (an island off the coast of Massachusetts) was thirty times that of the mainland population. Most deaf islanders were descendants of a small handful of English families who settled there around 1700.