International HapMap Project

• a catalog of common human genetic variants —— SNPs or single base pair indels

  • occur in both coding and non-coding region

  • distributed within and across populations

  • may contribute to disease or other phenotype due to small effect on

    • function of protein (if in coding region)

    • regulation of gene expression (if in non-coding region)

• Hap stands for haplotype

  • a combination of alleles that located closely tgt on the same chromosome and that tend to be inherited tgt

  • crossover may split alleles→ more variation

  • linkage disequilibrium (LD)

    • the phenomenon that variants close in distance segregate together and the genotypes are correlated

    • delays by genetic distance as chance of recombination increases

    • recombinant hot-spot: no LD between alleles

    • haplotype block: region of high LD between alleles

Type of genetic variation

• by nature

  • single nucleotide variation

  • insertion, deletion

  • copy number variation

  • structural variation

• by minor allele frequency (MAF) in the population

  • mutation or rare DNA variation: MAF<1%

  • polymorphism: MAF>1%

  • common polymorphismL MAF ≥5%

What HapMap Project study

• population-specific variants

• allele frequencies

• linkage disequilibrium pattern

• haplotype information

• tag SNPs

  • single nucleotide polymorphisms (SNPs) used to represent other SNPs in a region.

  • They help identify genetic variations across populations efficiently.

Importance of HapMap

• LD patterns: reduce type for genotype and analyse SNPs

• population-specific LD map: select tag SNPs for genotyping and reduce number SNPs genotyped and tested

• accelerate GWAS to design high density SNP arrays

Genome-wide association study (GWAS)

• Aim

  • Identifying associations through indirect tagging of causal variants in linkage disequilibrium.

• Linkage / association studies

  • when an SNP is close to the disease gene→ likely to be transmitted with the disease: linked or in linkage disequilibrium

  • markers can be used to identify mutations or variants that cause the disease or affect other trait via indirect association

  • the “associated“ SNP are physically linked and transmitted with the functional DNA variant that may lead to disease→ can help us locate the DNA variant

• compare the frequency of genetic markers between patients and controls

  • → markers more frequent in patients than in control = “associated with the disease“

GTEx Project

• Genotype-Tissue Expression (GTEx) Project

• Aim: To study how genetic variation influences gene expression across different human tissues.

• Samples collected from deceased donors across multiple tissues.

• Collected data is analysed via genotyping, RNA sequencing, and analysis of gene expression patterns.

• Findings: Revealed tissue-specific gene expression patterns and how genetic variants impact gene regulation.