Haplotypes

Haplotype is a contraction for haploid genotype.

It refers to a collection of specific alleles in a cluster of tightly-linked genes. The tighter the linkage, the less likely that the collection of alleles will be broken up by recombination; that is, the more likely that the haplotype will be preserved through subsequent generations.

A classic example is the cluster of HLA alleles in the major histocompatibility complex (MHC).

Even segments of DNA that lie between genes can be present as specific haplotypes.

Example 1

The many short tandem repeats (STRs) in the human genome.

STRs are repeated sequences of a few (usually four) nucleotides, e.g., TCATTCATTCATTCAT. They often occur in the untranslated parts of known genes (whose sequence can be used for the PCR primers). The exact number of repeats (6, 7, 8, 9, etc.) varies in different people (and, often, in the gene on each chromosome; that is, they carry two different haplotypes of that location).

Example 2

The >one million (106) single nucleotide polymorphisms (SNPs) in the human genome.

As the name suggests, SNPs are single base-pair changes that are found at certain locations on a chromosome in >1% of the population [Link]. Thus they do not include rare point mutations.

The HapMap Project

The International HapMap Consortium reported in the 27 October 2005 issue of Nature the location of >1 million SNPs in the human genome. These were found by sequencing the DNA of all 22 autosomes, the X and Y chromosomes, and the mitochondrial DNA from 169 people drawn from populations living in Nigeria (90), Utah (90), China (45), and Japan (40). The Nigerian and Utah populations were made up of 30 parent-offspring groups of three.

They discovered that a particular SNP is usually associated with a number of other SNPs forming a block inherited together — a haplotype.

Because of this tendency of a particular set of SNPs to remain together, called linkage disequilibrium, one can use one probe for a single SNP (called a "tag SNP") to search for the presence of the complete haplotype.

The procedure:

Haplotype analysis is now widely used in forensic work to Tracing family relationships is aided greatly by the presence of STRs and SNPs on

The Y Chromosome

Except for the few genes in the pseudoautosomal regions, no recombination takes place in the Y chromosome. Although the Y chromosome is something of a gene desert, it does contain STRs and SNPs, and the length of these remains constant for long periods.

Because the Y chromosome is transmitted from fathers to sons (only), STR/SNP polymorphism; that is, a particular STR/SNP haplotype, can be used to trace genealogy back through the male line. Several commercial organizations now offer haplotype analysis. Many African-American males have taken advantage of this to trace their ancestry. For example, the company can compare a haplotype with their database of haplotypes common in the different regions of Africa.

Mitochondrial DNA

A similar situation exists for mitochondrial DNA, but in this case it applies to females. Because

analysis of the pattern of STRs in the mitochondrial DNA of a woman can be used to trace her ancestry back through the female line.

Link to the example of "Mitochondrial Eve".

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20 September 2012