A genetic study of an early onset form of heart disease ...

Question

A genetic study of an early onset form of heart disease identifies 10 families containing members with the condition. No clear dominant or recessive pattern of inheritance is evident, but an analysis of SNP markers for five families detects a strong association with a marker on chromosome 12, and genetic linkage analysis for the marker produces a lod score of 2.2.

What next step do you recommend for this genetic analysis?

Accepted Answer

Hi, everyone. Let's take a look at this practice problem together. A genetic study of a rare autoimmune disease identified 20 affected individuals from 10 unrelated families. The disease shows autosomal recessive inheritance pattern but no mutation has been found in the known genes responsible for the disease. Whole genome sequencing was conducted in five affected individuals and 10 unaffected individuals from the same population. A bioinformatics analysis showed a novel variant in a gene on chromosome six to be present in all affected individuals but not in unaffected individuals. The variant is predicted to be deleterious and affect the function of the encoded protein. The genetic linkage analysis for the variant showed A L O D score of 3.1. What is the most appropriate next step for this genetic analysis? The answer options are a conduct R N A sequencing to validate the expression of the gene in affected individuals. Option B conduct a functional study to confirm the pathogenicity of the variant. Option. C analyze more individuals to increase the L O D score and D repeat the bioinformatics analysis with a different software tool. So to answer this question, we need to know what the L O D score is and what the number 3.1 means. So L O D is short for the logarithm of odds. It's a statistical term, it's an estimate of the likelihood that two different loci are likely to be near each other on the same chromosome and thus likely to be inherited together. Now, in a very simplified summary of the formula, I've put that on the screen and the L O D equals the odds that there's linkage divided by odds that there is no linkage. Now, L O D scores that are greater than or equal to three are considered statistically significant and evidence that linkage is occurring. So for our problem, A L O D score of 3.1 indicates that there is linkage between the variant gene and the diseases associated gene conducting R N E sequencing, analyzing more individuals and repeating bioinformatics analysis would further increase the evidence for linkage for linkage, but it would not provide any new information. A functional study, however, would study the genes function and confirm the pathogenicity of the variant. It would also help in next steps such as diagnosis of the disease and treatment. Therefore, the correct answer is option B conduct a functional study to confirm the pathogenicity of the variant. All right, everyone. I hope you found this helpful and I'll see you soon for the next practice problem.

Key Concepts

SNP Markers

Lod Score

Genetic Linkage Analysis

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