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Bombay Blood Group Phenotype
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Blunt-End Ligation
The three major complications are chronic lung disease, diabetes mellitus, and cancer. BS is a genetically determined trait transmitted in straightforward autosomal recessive fashion, mutation at the locus BLM being responsible. Homozygosity or compound heterozygosity of any of the more than 60 mutations at BLM identified so far result in a similar phenotype. The mutations are predominantly null alleles, but missense mutations also have been detected. BS is rare in all populations, but in the Ashkenazi Jewish population one particular mutant allele, a 6-bp deletion and 7-bp insertion that results in premature termination of translation, has through founder effect reached a relatively high carrier frequency of approximately 1%; in 31% of all persons with BS one or both parents are Ashkenazi. The genome is abnormally unstable in the somatic cells of persons with BS so that mutations arise spontaneously and accumulate in numbers many times greater than normal. These include both microscopically visible chromatid gaps, breaks, and rearrangements and mutations at specific loci. Exchanges between chromatids take place excessively, at what appear to be homologous sites. One consequence of this hyperrecombinability is reduction to homozygosity of constitutionally heterozygous loci distal to points of exchange. Some of the clinical characteristics of BS may be viewed as direct or indirect consequences of the hypermutability, so that clinical BS has been considered the prototype of a class of disease referred to as the somatic mutational disorders. Nevertheless, the small size, the diabetes, and the immunodeficiency remain to be explained. A major consequence of the hyperrecombinability and hypermutability is proneness to neoplasia; BS more than any other known human state predisposes to the development of cancer of the types and sites that affect the general population, and at unusually early ages: carcinoma commonest, leukemia and lymphoma next in frequency, the rare childhood neoplasms last. Diagnosis of BS is based on clinical observation. Laboratory confirmation ordinarily is by cytogenetic demonstration of the characteristically increased tendency of chromatid exchange to take place. BS is the only condition known that features a greatly increased rate of sister chromatid exchange (SCE), and blood lymphocytes in short-term culture are suitable for confirming or disaffirming the diagnosis. Under certain circumstances, the diagnosis can be confirmed by demonstrating mutation(s) at BLM by molecular techniques. The mapping of BLM to chromosome band 15q26.1 and its subsequent molecular isolation identified a nuclear protein which contains a 350 amino acid
domain common to DNA and RNA helicases. The helicase domain of the BLM protein is 40±45% identical to that present in the RecQ subfamily of DNA helicases. Although DNA-dependent ATPase activity and DNA duplex-unwinding activity have been demonstrated for several RecQ helicases including BLM, the nucleic acid substrates these proteins act upon in the cell are unknown. Whatever these substrates are, the molecular and genetic evidence from BS identify BLM as a protein of importance in the cellular mechanisms that maintain genomic stability.
Further Reading
German J (1993) Bloom syndrome: a Mendelian prototype of somatic mutational disease. Medicine 72: 393±406. German J and Ellis NA (2000) Bloom syndrome. In: Shriver CR, Beaudet AL, Sty WS and Valle D (eds) Metabolic and Molecular Bases in Inherited Disease, 8th edn, pp. 733±752. New York: McGraw-Hill.
See also: Genetic Diseases
Blunt-End Ligation Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1775
Blunt-end ligation is a reaction that joins two doublestranded DNA molecules (without `staggered cohesive ends') directly at their ends. See also: DNA Ligases
Bombay Blood Group Phenotype G Daniels Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0138
The Bombay phenotype is a very rare histo-blood group phenotype in which H antigen, the precursor of the A and B blood group antigens, is absent from red cells and from all other parts of the body. A and B antigens are not produced, regardless of ABO genotype. Bombay phenotype results from homozygosity for inactivating mutations in both 1,2-afucosyltransferase genes, FUT1 and FUT2. See also: Blood Group Systems
Blunt-End Ligation
The three major complications are chronic lung disease, diabetes mellitus, and cancer. BS is a genetically determined trait transmitted in straightforward autosomal recessive fashion, mutation at the locus BLM being responsible. Homozygosity or compound heterozygosity of any of the more than 60 mutations at BLM identified so far result in a similar phenotype. The mutations are predominantly null alleles, but missense mutations also have been detected. BS is rare in all populations, but in the Ashkenazi Jewish population one particular mutant allele, a 6-bp deletion and 7-bp insertion that results in premature termination of translation, has through founder effect reached a relatively high carrier frequency of approximately 1%; in 31% of all persons with BS one or both parents are Ashkenazi. The genome is abnormally unstable in the somatic cells of persons with BS so that mutations arise spontaneously and accumulate in numbers many times greater than normal. These include both microscopically visible chromatid gaps, breaks, and rearrangements and mutations at specific loci. Exchanges between chromatids take place excessively, at what appear to be homologous sites. One consequence of this hyperrecombinability is reduction to homozygosity of constitutionally heterozygous loci distal to points of exchange. Some of the clinical characteristics of BS may be viewed as direct or indirect consequences of the hypermutability, so that clinical BS has been considered the prototype of a class of disease referred to as the somatic mutational disorders. Nevertheless, the small size, the diabetes, and the immunodeficiency remain to be explained. A major consequence of the hyperrecombinability and hypermutability is proneness to neoplasia; BS more than any other known human state predisposes to the development of cancer of the types and sites that affect the general population, and at unusually early ages: carcinoma commonest, leukemia and lymphoma next in frequency, the rare childhood neoplasms last. Diagnosis of BS is based on clinical observation. Laboratory confirmation ordinarily is by cytogenetic demonstration of the characteristically increased tendency of chromatid exchange to take place. BS is the only condition known that features a greatly increased rate of sister chromatid exchange (SCE), and blood lymphocytes in short-term culture are suitable for confirming or disaffirming the diagnosis. Under certain circumstances, the diagnosis can be confirmed by demonstrating mutation(s) at BLM by molecular techniques. The mapping of BLM to chromosome band 15q26.1 and its subsequent molecular isolation identified a nuclear protein which contains a 350 amino acid
domain common to DNA and RNA helicases. The helicase domain of the BLM protein is 40±45% identical to that present in the RecQ subfamily of DNA helicases. Although DNA-dependent ATPase activity and DNA duplex-unwinding activity have been demonstrated for several RecQ helicases including BLM, the nucleic acid substrates these proteins act upon in the cell are unknown. Whatever these substrates are, the molecular and genetic evidence from BS identify BLM as a protein of importance in the cellular mechanisms that maintain genomic stability.
Further Reading
German J (1993) Bloom syndrome: a Mendelian prototype of somatic mutational disease. Medicine 72: 393±406. German J and Ellis NA (2000) Bloom syndrome. In: Shriver CR, Beaudet AL, Sty WS and Valle D (eds) Metabolic and Molecular Bases in Inherited Disease, 8th edn, pp. 733±752. New York: McGraw-Hill.
See also: Genetic Diseases
Blunt-End Ligation Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1775
Blunt-end ligation is a reaction that joins two doublestranded DNA molecules (without `staggered cohesive ends') directly at their ends. See also: DNA Ligases
Bombay Blood Group Phenotype G Daniels Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0138
The Bombay phenotype is a very rare histo-blood group phenotype in which H antigen, the precursor of the A and B blood group antigens, is absent from red cells and from all other parts of the body. A and B antigens are not produced, regardless of ABO genotype. Bombay phenotype results from homozygosity for inactivating mutations in both 1,2-afucosyltransferase genes, FUT1 and FUT2. See also: Blood Group Systems