A study is undertaken to map the HLA-DQ loci in a population with a high incidence of celiac sprue. High-resolution HLA typing of the DQA1 and DQB1 loci is performed using polymerase chain reaction sequencing. The frequency of the DQA1*0501-DQB1*0201 haplotype, strongly implicated in autoimmunity, is found to be 0.2. However, in the same population, the frequency of the DQA1*0501 allele is 0.3 and the frequency of the DQB1*0201 allele is 0.2. Which of the following best explains the observed DQA1*0501-DQB1*0201 haplotype frequency in this population?

Question

A study is undertaken to map the HLA-DQ loci in a population with a high incidence of celiac sprue.  High-resolution HLA typing of the DQA1 and DQB1 loci is performed using polymerase chain reaction sequencing.  The frequency of the DQA1*0501-DQB1*0201 haplotype, strongly implicated in autoimmunity, is found to be 0.2.  However, in the same population, the frequency of the DQA1*0501 allele is 0.3 and the frequency of the DQB1*0201 allele is 0.2.  Which of the following best explains the observed DQA1*0501-DQB1*0201 haplotype frequency in this population?

Quizplus · Accepted Answer

11ec160b_376c_057d_9249_f9fcd9df346a_MD0001_00 Two genetic loci are said to be in linkage disequilibrium when their respective alleles are inherited together in the same gamete (haplotype) more or less often than expected by chance alone given their corresponding allele frequencies. Although linkage disequilibrium is often the result of physical proximity of genes on the same chromosome, it does not always imply physical linkage between the allelic loci. To estimate the expected probability of 2 alleles from separate loci appearing together, multiply their occurrence rates. Note that the Hardy-Weinberg principle (2pq) is not applicable when considering alleles at different loci. 11ec160b_376c_057e_9249_373ad3b3ae33_MD0001_00 In this example, the observed frequency of both alleles being inherited together is 0.2, which is greater than the expected frequency of 0.06; therefore, the population is said to be in linkage disequilibrium. This disequilibrium is explained by the close proximity of the HLA-DQA1 and HLA-DQB1 loci that code for α and β chains of class II major histocompatibility complex. (Choice A) Heteroplasmy describes the presence of different mitochondrial genomes (eg, mutated and wild type) within a single cell. The severity of mitochondrial diseases is often related to the proportion of abnormal to normal mitochondria. (Choice B) Penetrance is the proportion of people with a given genotype who express its associated phenotype. If all individuals with a given gene express its phenotype, that gene is said to have full penetrance. (Choice D) Pleiotropy is the occurrence of multiple phenotypic manifestations, often in different organ systems, which result from a mutation in a single gene. (Choice E) The law of segregation describes the phenomenon in which gametogenesis results in the separation of paired chromosomes so that the offspring inherit only half of each parent's genetic composition. Educational objective: Two allele loci are said to be in linkage disequilibrium when a pair of alleles are inherited together in the same gamete (haplotype) more often or less often than would be expected given random pairing. This most often occurs when the genes are in close physical proximity on the same chromosome. __________ References: Gene polymorphisms, inflammatory diseases and cancer. (http://www.ncbi.nlm.nih.gov/pubmed/12691174) Linkage disequilibrium and its expectation in human populations. (http://www.ncbi.nlm.nih.gov/pubmed/19210178)

A Study Is Undertaken to Map the HLA-DQ Loci in a Population