Homozygosity haplotype allows a genomewide search for the autosomal segments shared among patients

Am J Hum Genet. 2007 Jun;80(6):1090-102. doi: 10.1086/518176. Epub 2007 May 2.


A promising strategy for identifying disease susceptibility genes for both single- and multiple-gene diseases is to search patients' autosomes for shared chromosomal segments derived from a common ancestor. Such segments are characterized by the distinct identity of their haplotype. The methods and algorithms currently available have only a limited capability for determining a high-resolution haplotype genomewide. We herein introduce the homozygosity haplotype (HH), a haplotype described by the homozygous SNPs that are easily obtained from high-density SNP genotyping data. The HH represents haplotypes of both copies of homologous autosomes, allowing for direct comparisons of the autosomes among multiple patients and enabling the identification of the shared segments. The HH successfully detected the shared segments from members of a large family with Marfan syndrome, which is an autosomal dominant, single-gene disease. It also detected the shared segments from patients with model multigene diseases originating with common ancestors who lived 10-25 generations ago. The HH is therefore considered to be useful for the identification of disease susceptibility genes in both single- and multiple-gene diseases.

MeSH terms

  • Age Factors
  • Alleles
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human*
  • Computer Simulation
  • Disease Susceptibility
  • False Positive Reactions
  • Gene Frequency
  • Genes, Dominant
  • Genome, Human*
  • Genotype
  • Haplotypes*
  • Homozygote*
  • Humans
  • Marfan Syndrome / genetics
  • Pedigree
  • Polymorphism, Single Nucleotide