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Meckel Gruber syndrome is a rare autosomal recessive lethal disorder with wide spectrum of clinical manifestations.
To investigate how many recessive lethal mutations are carried by humans on average, Ziyue Gao, a graduate student in the Genetics, Genomics and Systems Biology program, and her colleagues worked closely with a group of Hutterites, a religious community that settled in North America in the 1870s.
DMD is the most common X-linked recessive lethal disease, with an incidence of approximately 1 in 3500 newborns (1).
We don't yet understand why the number of recessive lethal mutations might be relatively constant across distantly related organisms," said Gao.
If a "recessive lethal mutation" is defined as a mutation that results mainly in the premature death of homozygous individuals, sickle cell anemia is a recessive lethal condition.
However, it is not yet known whether the genetic load revealed by inbreeding is composed primarily of genes that would respond readily to that selection (such as recessive lethal alleles), primarily of genes that would not respond readily to selection (such as a genes showing overdominant fitness effects or genes with individually small effects), or different genetic bases in different populations.
We suggest a simple experimental design in which natural selection acts against a phenotypically visible conditional recessive lethal, thus allowing observation of significant allele frequency changes in just a few generations.
The recessive lethal genes that are scattered through a population begin to come together and you start to see problems.
Selection is multiplicative across loci, so that a genotype with i heterozygous recessive lethal mutations has a relative fitness of [Mathematical Expression Omitted], where h is the dominance coefficient and the mean fitness in the population.
If inbreeding depression is the product of recessive lethal and deleterious alleles that are maintained by mutation-selection balance, then inbreeding depression at equilibrium should decline with increased inbreeding (Lande and Schemske 1985; Charlesworth and Charlesworth 1987; Waller 1993).
According to the partial-dominance hypothesis, the cause of lower fitness of progeny derived from inbreeding as compared with outcrossing is the exposure of recessive or nearly recessive lethal and deleterious mutations in the inbred offspring.