Preparatory Mindset

Study this chapter with focus on how genetic principles affect clinical practice.

Core Concepts

• LOD score: Log of odds ratio for linkage. LOD >3 = significant linkage (odds >1000:1); LOD <-2 = linkage excluded


• Parametric linkage: Requires specifying inheritance model (AD/AR/XR, penetrance, allele frequency)


• Non-parametric linkage: No model needed (affected sib pair analysis)


• GWAS: Genome-wide association study — tests millions of SNPs for association with complex traits


• Candidate gene approach: Test genes with known biological relevance to the disease


• Fine mapping: Narrow the linked chromosomal region to identify the causal gene


• Association study: Case-control comparison of allele frequencies at a locus


• Positional cloning: Identify disease gene based on its chromosomal location (not function)

High-Yield Points

• LOD >3 = linkage established; LOD <-2 = linkage excluded


• Parametric = known model; Non-parametric = no model needed


• GWAS for complex traits; Linkage for Mendelian disorders

Topic Summary

Identifying disease genes uses linkage analysis (for Mendelian disorders) and association studies (for complex traits). LOD scores measure evidence for linkage.