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Studies on human genome variation provide insight into disease

ant hereditary component to the disease, and one of the most strongly associated genomic regions lies on the X chromosome.

This X chromosomal region spans a cluster of five SPANX genes that are predominantly expressed in the testis and in certain tumors. In this month's issue of Genome Research, Dr. Vladimir Larionov and his colleagues examined the genetic architecture of the SPANX cluster and showed how the region exhibited dynamic deletions, duplications, and gene conversion events, some of which may have resulted in the development of mutations involved in prostate cancer susceptibility.

"Because of the strong similarity among genes in this region, we had to develop a new technique for our mutational analysis, which we call TAR cloning," explains Larionov. "Using this method, we isolated the SPANX region from 200 individuals by recombination in yeast."

Based on their results, the authors speculate that predisposition to prostate cancer ?at least in some individuals ?is determined by the specific architecture of the SPANX gene cluster on the X chromosome. "We're hoping to clarify which specific types of genomic rearrangements lead to prostate cancer susceptibility," says Larinov, "so that we can someday identify therapeutic targets for this disease."

Contact:
Vladimir Larionov, Ph.D.
Head, Genome Structure and Function Section, National Cancer Institute
Phone: 301-496-7941
E-mail: larionov@mail.nih.gov

Genetic traffic in DiGeorge syndrome

One of the most common human genomic disorders, DiGeorge syndrome, occurs in one of every 2,000-4,000 live births and involves a deletion on chromosome 22. The deletion is mediated by rare repetitive sequences that flank genes crucial for proper development of the heart, face, and upper thorax.

Dr. Bernice Morrow and her colleagues describe in this month'
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Source:Cold Spring Harbor Laboratory


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