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Small population sizes put a species at extreme risk of extinction due to a lack of variation, and a consequent decrease in adaptability. This weakens the chances of survival under pressures such as climate change, competition from other species, or new diseases. Large populations are more likely to survive pressures such as these, as such populations are more likely to harbor individuals that have genetic variants that are adaptive under new stresses. Small populations are much less likely to have such variation.

Modern genomic techniques can identify homozygosity in deleterious genes that is caused by inbreeding. This happens when closely-related organisms produce offspring; the offspring have a higher chance of receiving two identical deleterious alleles. For example, the wolves in Isle Royale National Park went through an extreme population reduction caused by a disease outbreak, which led to increased inbreeding. The wolf population has continued to decline, at one point containing only two wolves.

Whole-genome sequencing allowed researchers to identify the lineage of the remaining wolves on Isle Royale, which showed sibling-sibling and parent-offspring matings in the small population based on patterns of chromosomal inheritance. Analysis of gene sequences showed deleterious single-nucleotide polymorphisms (SNPs) within functional genes that reduce the fitness of these wolves. These mutations explain physical characteristics that can be seen in Isle Royale wolves, such as malformations in their spines and rib cages.

Park rangers are bringing in wolves from outside the park to establish healthy genetic diversity on Isle Royale. Given a healthier, larger population, the wolves should be able to thrive on Isle Royale. Rangers also track the wolves on the island with GPS collars to determine if their conservation methods are effective.