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Susceptibility Of TB In Humans Might Be Due To Three Human Gene Variants

A new study has reported that there appears to be three variations of a human gene that seem to cause an impact on humans upon their susceptibility towards tuberculosis// . Researchers hope that these findings would provide sufficient knowledge as to why some patients infected with the Mycobacterium tuberculosis pathogen develop the full-blown disease while others are seemingly not affected. The findings was published in the online edition of the Proceedings of the National Academy of Sciences (PNAS) (http://www.pnas.org/) for the week of June 19-23,

The paper additionally describes how the association of two of the gene variants with the disease has been replicated.

Approximately one-third of the world's population is thought to be infected with the M. tuberculosis pathogen, yet only about 10 percent becomes ill with the active disease. Researchers suspect that a variety of factors interplay to determine who develops the full-blown disease. For example, in February 2006 Harvard School of Public Health (HSPH) researchers were part of a team that identified a mechanism that explains why people of African descent may be more vulnerable to the disease.
(http://www.hsph.harvard.edu/press/
releases/press02232006B.html)

Now HSPH Associate Professor Igor Kramnik is part of a team led by Professor Adrian V.S. Hill of Oxford University that has identified three variations of a human gene associated with tuberculosis susceptibility. The lead author on the paper is Kerrie Tosh of the Welcome Trust Centre for Human Genetics in the U.K.

Kramnik and his colleagues had previously identified a gene in mice called Ipr1 (intracellular pathogen resistance 1) that plays a significant role in limiting the multiplication of intracellular pathogens M. tuberculosis and Listeria monocytogenes inside host cells.
(http://www.hsph.harvard.edu/press/
releases/press04062005.html)

The Hill team then examined the closest ho molog of the mouse gene Ipr1 that can be found in humans--a gene called SP110. Three variations of the SP110 gene were found to be associated with tuberculosis in humans.

The variations of SP110 emerged from an analysis of 20 pieces of genetic material called SNPs that were culled from an original set of 27 SNPs taken from samples provided by 219 families in The Gambia. Two of the variations and their association with tuberculosis were further replicated in samples from 99 families in the Republic of Guinea and 102 families in Guinea-Bissau.
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