A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer
- Georgetown Univ. School of Medicine, Washington, DC (United States)
- Children's Hospital, Boston, MA (United States) Harvard Medical School, Boston, MA (United States)
- Univ. of California, Los Angeles (United States) Veterans Administration Medical Center, Los Angeles, CA (United States)
- National Cancer Inst., Bethesda, MD (United States)
The poly(ADP-ribose) polymerase (PADPRP) gene (13q33-qter) depicts a two-allele (A/B) polymorphism. In the noncancer population, the frequency of the B allele is higher among blacks than among whites. Since the incidence of multiple myeloma and prostate and lung cancer is higher in the US black population, the authors have analyzed the B-allele frequency in germ-line DNA to determine whether the PADPRP gene correlates with a polymorphic susceptibility to these diseases. For multiple myeloma and prostate cancer, an increased frequency of the B allele appeared to be striking only in black patients. In contrast, the distribution of the B allele in germ-line DNA did not differ among white patients with these diseases, when compared with the control group. An elevated B-allele frequency was also found in germ-line DNA in blacks with colon cancer. These observations suggest that the PADPRP polymorphism may provide a valid marker for a predisposition to these cancers in black individuals. To determine the genomic structure of the polymorphic PADPRP sequences, a 2.68-kb HindIII clone was isolated and sequenced from a chromosome 13-enriched library. Sequence analysis of this clone (A allele) revealed a close sequence similarity (91.8%) to PADPRP cDNA (1q42) and an absence of introns, suggesting that the gene on 13q exists as a processed pseudogene. A 193-bp conserved duplicated region within the A allele was identified as the source of the polymorphism. The nucleotide differences between the PADPRP gene on chromosome 13 and related PADPRP genes were exploited to develop oligonucleotides that can detect the difference between the A/B genotypes in a PCR. This PCR assay offers the opportunity for analyzing additional black cancer patients, to determine how the PADPRP processed pseudogene or an unidentified gene that cosegregates with the PADPRP gene might be involved with the development of malignancy. 16 refs., 6 figs., 1 tab.
- OSTI ID:
- 6613528
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 52:1; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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HUMAN CHROMOSOMES
MAPPING
NEOPLASMS
POLYMERASES
RFLPS
ADP
DISTRIBUTION
DNA
DNA SEQUENCING
GENES
LARGE INTESTINE
LUNGS
OLIGONUCLEOTIDES
PROSTATE
RIBOSE
ALDEHYDES
BODY
CARBOHYDRATES
CHROMOSOMES
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GASTROINTESTINAL TRACT
GLANDS
INTESTINES
MALE GENITALS
MONOSACCHARIDES
NUCLEIC ACIDS
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANS
PENTOSES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RESPIRATORY SYSTEM
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
550400* - Genetics