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genetic variations

Friday 30 September 2005

The existence of molecular genetic variation among human populations was first demonstrated by Hirszfeld and Hirszfeld1 in a classic study published in 1919 of the first human gene to be described-ABO, which determines ABO blood groups.

The subsequent identification of blood group protein markers, such as MNS and Rh expanded the repertoire of polymorphic markers that could be analyzed using antibodies.

R.A. Fisher showed that evolution could be reconstructed by analyzing the multilocus genotypes on a chromosome observed in populations and their inheritance within families.

It was soon obvious that genetic variation was not rare but, on the contrary, that almost every protein had genetic variants. These variants became useful markers for population studies.

The first book of allele frequencies in populations, published in 1954, was limited almost completely to serological variation, and books listing genetic variation increased rapidly in size and number.

In 1980, a method for studying variation in DNA identified mutants of restriction sites by using radioisotopes and generated several new markers.

But it was only with the development of PCR in 1986 that the study of more general DNA variation became possible.

The development of automated DNA sequencing in the early 1990s paved the way for the application of systematic study of genome variation to human evolutionary biology.

Data from protein markers (sometimes called ’classical’ markers) are still more abundant than are data from DNA, although this situation is rapidly changing.

For example, Rosenberg et al. studied 377 autosomal microsatellite polymorphisms in 1,065 individuals from 52 populations producing a total of 4,199 different alleles, about half of which were found in all principal continental regions.

Another study of 3,899 single-nucleotide polymorphisms (SNPs) in 313 genes sampled in 82 Americans self-identified as African American, Asian, European or Hispanic Latino found that only 21% of the sites were polymorphic in all four groups-a fraction that would be expected to increase with more sampled individuals.

It is interesting to note, however, that so far no conclusions derived from the earlier studies of classical polymorphisms14 have been found to be in disagreement with those obtained with DNA markers.

Nonetheless, molecular genetic markers have provided previously unavailable resolution into questions of human evolution, migration and the historical relationship of separated human populations.

Evolutionary and historical forces have shaped genomic variation and its interpretation has led to a deeper understanding of the evolution of our species.

All genetic variation is caused by mutations, of which there are many different types. The most common and most useful for many purposes are SNPs, which can be detected by DNA sequencing and other recently developed methods, such as denaturing high performance liquid chromatography, mass spectrometry and array-based resequencing.


- Human Genome Variation Society (The Society aims to foster discovery and characterization of genomic variations including population distribution and phenotypic associations.)


- Marjoram P, Tavare S. Modern computational approaches for analysing molecular genetic variation data. Nat Rev Genet. 2006 Oct;7(10):759-70. PMID: 16983372

- Cavalli-Sforza LL, Feldman MW. The application of molecular genetic approaches to the study of human evolution. Nat Genet. 2003 Mar;33 Suppl:266-75. PMID: 12610536