Linkage disequilibrium in the human genome

Area of Science:

• Human Genetics
• Population Genetics
• Genomic Mapping

Background:

• Dense genome-wide maps of single nucleotide polymorphisms (SNPs) raise the possibility of using linkage disequilibrium (LD) for disease gene mapping.
• The extent of LD blocks, crucial for mapping resolution, has been debated, with estimates ranging from a few kilobases (kb) to over 100 kb.

Purpose of the Study:

• To systematically investigate the extent of LD across multiple genomic regions using a uniform protocol.
• To determine the feasibility of LD mapping for disease genes in different populations.

Main Methods:

• Examined 19 randomly selected genomic regions using a uniform experimental protocol.
• Analyzed LD patterns in a North American population of North-European descent and a Nigerian population.

Main Results:

• In the North-European descent population, LD typically extends approximately 60 kb from common SNPs, suggesting LD mapping is practical.
• LD extends significantly less in the Nigerian population compared to the North-European descent population.
• Observed LD patterns in Northern Europeans suggest influence from a demographic event 27,000–53,000 years ago.

Conclusions:

• LD mapping is a potentially practical approach for disease gene discovery in populations with extensive LD, such as those of North-European descent.
• Differences in LD extent between populations provide insights into human evolutionary history and demographic events.