Imperial College London

ProfessorAnneBowcock

Faculty of MedicineNational Heart & Lung Institute

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 1511a.bowcock

 
 
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Location

 

Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

225 results found

Bowcock AM, Ruiz-Linares A, Tomfohrde J, Minch E, Kidd JR, Cavalli-Sforza LLet al., 1994, High resolution of human evolutionary trees with polymorphic microsatellites., Nature, Vol: 368, Pages: 455-457, ISSN: 0028-0836

Genetic variation at hypervariable loci is being used extensively for linkage analysis and individual identification, and may be useful for inter-population studies. Here we show that polymorphic microsatellites (primarily CA repeats) allow trees of human individuals to be constructed that reflect their geographic origin with remarkable accuracy. This is achieved by the analysis of a large number of loci for each individual, in spite of the small variations in allele frequencies existing between populations. Reliable evolutionary relationships could also be established in comparisons among human populations but not among great ape species, probably because of constraints on allele length variation. Among human populations, diversity of microsatellites is highest in Africa, which is in contrast to other nuclear markers and supports the hypothesis of an African origin for humans.

Journal article

Bowcock AM, Tomfohrde J, Weissenbach J, Bonne-Tamir B, St George-Hyslop P, Giagheddu M, Cavalli-Sforza LL, Farrer LAet al., 1994, Refining the position of Wilson disease by linkage disequilibrium with polymorphic microsatellites., Am J Hum Genet, Vol: 54, Pages: 79-87, ISSN: 0002-9297

Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed.

Journal article

Bowcock AM, 1993, Molecular cloning of BRCA1: a gene for early onset familial breast and ovarian cancer., Breast Cancer Res Treat, Vol: 28, Pages: 121-135, ISSN: 0167-6806

Molecular analyses allow one to determine genetic lesions occurring early in the development of tumors. With positional cloning approaches we are searching for a gene involved in the development of early onset familial breast and ovarian cancer that maps to human chromosome 17q21 and is termed BRCA1. This involves localizing the region genetically within families with multiply affected members, capturing the region identified by genetic analyses in YACs (yeast artificial chromosomes), converting those YACs to smaller manipulable pieces (such as cosmids), and searching for genes via a variety of approaches such as direct screening of cDNA libraries with genomic clones, direct selection by hybridization, "exon trapping", and CpG island rescue. Once identified, candidate genes will be screened for mutations in affected family members in whom breast cancer segregates with the locus on 17q21. The frequency of this gene has been calculated to be 0.0033; from this the incidence of carriers, i.e. those carrying such a predisposition, is one in 150 women. The isolation of BRCA1 and the elucidation of the mutations resulting in breast and ovarian cancer predisposition will allow identification of women who have inherited germ-line mutations in BRCA1. In families known to harbor a germ-line BRCA1 mutation, diagnosis of affected members will be rapid. It is possible that one will also be able to detect alterations of the second copy of this gene early in tumor development in individuals carrying a germ-line mutation. It is not yet known how frequently somatic BRCA1 mutations predispose to breast and ovarian carcinoma in the general female population. If, as in other genetic diseases, new germ-line mutations occur in some women and thus contribute to the development of breast cancer, it may be feasible to screen women in the general population for predisposing mutations. In addition, if acquired genetic mutations of the BRCA1 gene are involved as early events in the de

Journal article

Bowcock AM, Gerken SC, Barnes RI, Shiang R, Jabs EW, Warren AC, Antonarakis S, Retief AE, Vergnaud G, Leppert Met al., 1993, The CEPH consortium linkage map of human chromosome 13., Genomics, Vol: 16, Pages: 486-496, ISSN: 0888-7543

The CEPH consortium map of chromosome 13 is presented. This map contains 59 loci defined by genotypes generated from CEPH family DNAs with 94 different probe and restriction enzyme combinations contributed by 9 laboratories. A total of 25 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from loci in the centromeric region of chromosome 13 to the terminal band of the long arm. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 158, 203, and 178 cM respectively. The largest interval is 24 cM and is between D13Z1 (alpha RI) and ATP1AL1. The mean genetic distance between the 25 uniquely placed loci is 7 cM.

Journal article

Bowcock AM, Anderson LA, Friedman LS, Black DM, Osborne-Lawrence S, Rowell SE, Hall JM, Solomon E, King MCet al., 1993, THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21., Am J Hum Genet, Vol: 52, Pages: 718-722, ISSN: 0002-9297

In order to pinpoint the locale of the gene for early-onset familial breast and ovarian cancer (BRCA1), polymorphisms were developed within the locus for thyroid hormone receptor alpha (THRA1) and for several anonymous sequences at chromosome 17q12-q21. The THRA1 polymorphism is a dinucleotide repeat with 10 alleles and heterozygosity.79. Gene mapping in extended families with inherited, early-onset breast and ovarian cancer indicates that BRCA1 is distal to THRA1 and proximal to D17S183 (SCG43), an interval of < 4 cM. This locale excludes HER2, THRA1, WNT3, HOX2, NGFR, PHB, COLIA1, NME1, and NME2 as candidates for BRCA1 but does not exclude RARA or EDH17B. Resolving the remaining recombination events in these families by new polymorphisms in the THRA1-D17S183 interval will facilitate positional cloning of the breast-ovarian cancer gene on chromosome 17q12-q21.

Journal article

Easton DF, Bishop DT, Ford D, Crockford GPet al., 1993, Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium., Am J Hum Genet, Vol: 52, Pages: 678-701, ISSN: 0002-9297

Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist

Journal article

Bowcock A, Osborne-Lawrence S, Barnes R, Chakravarti A, Washington S, Dunn Cet al., 1993, Microsatellite polymorphism linkage map of human chromosome 13q., Genomics, Vol: 15, Pages: 376-386, ISSN: 0888-7543

Twelve polymorphic (CA)n microsatellites were isolated from a flow-sorted chromosome 13 genomic library. These, and two others that have been previously described, were genotyped in 41 families from the CEPH (Centre d'Etude Polymorphisme Humain, Paris), and a primary linkage map with considerable support for order (odds > 10,000:1) was constructed. Two RFLP-based markers, COL4A1 and D13S52, with heterozygosities above 0.67 and an RFLP-based centromeric marker at D13Z1 were included in this map which extends from 13cen to 13q34. The heterozygosity of all of the PCR-based markers is above 60%. The total map spans a genetic distance of 144 cM, extending from D13Z1 to D13S52 with a single maximum intermarker recombination distance of 35 cM. All other intermarker recombination distances are 18 cM or less. Marker order was confirmed by sublocalizing many of the microsatellite containing clones on a panel of rodent-human somatic cell hybrids with deletions and rearrangements of chromosome 13. One spontaneous new mutation for these 14 (CA)n repeat markers was identified from a total of 8006 gametes, giving an overall observed spontaneous mutation rate of 0.00012 per locus per gamete. An integrated map of chromosome 13q was constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. This sex-average map spans 209 cM with an average distance between unique map locations of 4.5 cM; the maximum intermarker distance was 14 cM.

Journal article

Bowcock A, 1993, Report of the First International Workshop on Human Chromosome 13 Mapping. Dallas, Texas, September 21-22, 1992., Cytogenet Cell Genet, Vol: 62, Pages: 89-107, ISSN: 0301-0171

Journal article

Kurth JH, Bowcock AM, Erlich HA, Cavallisforza LLet al., 1992, HLA-DQa allelic frequencies detected with PCR in a variety of human populations., Gene Geogr, Vol: 6, Pages: 175-183, ISSN: 0394-249X

Polymerase chain reaction (PCR) amplification and oligonucleotide probe hybridization may be used to detect DNA polymorphisms rapidly in large samples. In this study, 475 individuals from thirteen human populations were allelotyped at the human leukocyte antigen (HLA) DQa (DQA1) locus. A 242 or 239 bp fragment was amplified from each individual's DNA. Each of six alleles was detected by hybridization to allele specific oligonucleotide probes (ASOs). Allelic frequencies varied between populations, but the measure of gene frequency variation among populations, the FST value, was relatively low. Most populations had genotypic frequencies in agreement with Hardy-Weinberg equilibrium expectations. Principal component analysis was performed on the populations, and results are presented in graphic form. The heterozygosity at this locus is high in all populations; the average (74%) is close to the theoretical maximum (83%) for a 6 allele system. It is likely that this system is affected by stabilizing selection, which makes it less than optimal for the study of random evolutionary divergence between populations.

Journal article

Bowcock AM, Barnes RI, White RL, Kruse TA, Tsipouras P, Sarfarazi M, Jenkins T, Viljoen C, Litt M, Kramer PLet al., 1992, The CEPH consortium linkage map of human chromosome 15q., Genomics, Vol: 14, Pages: 833-840, ISSN: 0888-7543

The CEPH consortium map of chromosome 15q is presented. The map contains 41 loci defined by genotypes generated from CEPH family DNAs with 45 different probe and restriction enzyme combinations contributed by 10 laboratories. A total of 29 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from 15q13 to 15q25-qter. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 127, 190, and 158 cM, respectively. The largest interval is 21 cM and is between D15S37 and D15S74. The on-average locus spacing is 5.6 cM and the mean genetic distance between the 21 uniquely placed loci is 8 cM.

Journal article

Bowcock AM, Azuma T, Barnes RI, Wu SH, Bell GI, Taggart RTet al., 1992, Detection of a polymorphism within the pepsinogen C gene with PCR: construction of a linkage map around PGC from 6p11-6p21.3., Genomics, Vol: 14, Pages: 398-402, ISSN: 0888-7543

An insertion/deletion polymorphism between exons 7 and 8 of the pepsinogen C gene (PGC), previously detectable with Southern analysis, was formatted for detection with PCR. Alleles were rapidly typed by UV irradiation of ethidium bromide-stained agarose gels. Whereas Southern analysis revealed two alleles, the smaller fragments generated with PCR allowed the resolution of three alleles that were previously scored as a single allele and increased the heterozygosity of the system from 0.20 to 0.53. After a set of reference families was genotyped with the PCR-based polymorphism, a linkage map around the PGC gene on chromosome 6 was constructed. This included the HLA cluster and the highly informative D6S223 locus. PGC lies 22 cM proximal to HLA-DPB and between D6S5 and D6S4 at distances of 4.5 and 13.1 cM, respectively.

Journal article

Mountain JL, Lin AA, Bowcock AM, Cavalli-Sforza LLet al., 1992, Evolution of modern humans: evidence from nuclear DNA polymorphisms., Philos Trans R Soc Lond B Biol Sci, Vol: 337, Pages: 159-165, ISSN: 0962-8436

Previously we have described studies of the evolution of modern humans based upon data for classical genetic markers and for nuclear DNA polymorphisms. Such polymorphisms provide a different point of view regarding human evolution than do mitochondrial DNA sequences. Here we compare revised dates for major migrations of anatomically modern humans, estimated from archaeological data, with separations suggested by a genetic tree constructed from classical marker allele frequencies. Analyses of DNA polymorphisms have now been extended and compared with those of classical markers; genetic trees continue to support the hypothesis of an initial African and non-African divergence for modern humans. We have also begun testing non-human primates for a set of human DNA polymorphisms. For most polymorphisms tested so far, humans share a single allele with other primates; such shared alleles are likely to be ancestral. Populations living in humid tropical environments have significantly higher frequencies of ancestral alleles than do other populations, supporting the hypothesis that natural selection acts to maintain high frequencies of particular alleles in some environments.

Journal article

Bowcock A, Osborne-Lawrence S, Barnes R, Weiss L, Dunn Get al., 1992, Dinucleotide repeat polymorphism at the D6S223 locus., Hum Mol Genet, Vol: 1, ISSN: 0964-6906

Journal article

Bowcock AM, Hebert JM, Mountain JL, Kidd JR, Rogers J, Kidd KK, Cavalli-Sforza LLet al., 1991, Study of an additional 58 DNA markers in five human populations from four continents., Gene Geogr, Vol: 5, Pages: 151-173, ISSN: 0394-249X

One hundred DNA polymorphisms from 73 loci (42 genes and 31 anonymous DNA segments) were investigated in five populations (Biaka and Mbuti Pygmies, Melanesians, Chinese and Caucasoids). Data for 47 polymorphisms, including 42 of those discussed here, were described previously [Bowcock et al 1987]. Here we report statistical quantities of genetic importance for each gene and population. The average FST for the 100 markers is 0.137 and the average heterozygosity is 0.325. When known genes and anonymous segments are compared there is no significant difference in the average FST values or in the average heterozygosities.

Journal article

Bowcock AM, Farrer LA, Hebert JM, Bale AE, Cavalli-Sforza Let al., 1991, A contiguous linkage map of chromosome 13q with 39 distinct loci separated on average by 5.1 centimorgans., Genomics, Vol: 11, Pages: 517-529, ISSN: 0888-7543

A fine-structure linkage map of chromosome 13q is presented. This map contains 39 continuously linked loci defined by genotypes generated from the CEPH family DNAs with 56 probe and enzyme combinations. An alpha-satellite probe for sequences on chromosome 13 was included, resulting in a complete map of 13q with 39 distinct loci. The map spans 1.715 M in males and 2.099 M in females and the mean genetic distance between adjacent loci is 5.1 cM. Although there was generally a several-fold excess of female recombination in the interstitial portion of 13q, an excess of recombination in males was observed at both ends of this chromosomal arm. This map should be useful for the localization of any additional marker, gene, or disease locus of interest on chromosome 13q.

Journal article

Bowcock A, Cavalli-Sforza L, 1991, The study of variation in the human genome., Genomics, Vol: 11, Pages: 491-498, ISSN: 0888-7543

Regions of the genome showing high evolutionary stability are often conserved as a result of functional constraints. Conversely, more variable regions are likely to represent DNA with no functional or structural importance. However, as in the case of immunologically important regions, sequence divergence does not always indicate lack of functional importance. There is thus a wealth of information from both a functional and an evolutionary point of view that comes from studies of DNA sequence variation, a neglected aspect of the genome endeavor. Naturally, one cannot sequence hundreds of individuals in full, but a useful compromise is to use less expensive methods and to limit the more expensive types of analysis to an appropriately chosen sample of loci. The sample could be determined after careful consideration of categories of DNA segments with respect to individual variation. The study of such categories of DNA variation patterns can help in the understanding of the role of each gene and vice versa. One other important application requiring a study of DNA variation in different human populations is forensic DNA typing. This study requires a knowledge of allele frequencies in different human populations. Evidence of a match between two DNA samples is meaningless if the approximate population frequency of the DNA pattern is not known. It has been suggested (E. Lander) that one use the highest frequency for the most common allele as a baseline frequency estimate. Obviously, systems in which this is employed require an extensive analysis of population-specific allele frequencies. In general, the best way of studying interindividual variation when detecting or describing new polymorphisms is to include interethnic variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal article

Waber PG, Bowcock AM, Arencibia-Mireles O, Nisen PDet al., 1991, Nonrandom distribution of N-myc oncogene genotypes in neuroblastoma., J Natl Cancer Inst, Vol: 83, Pages: 1085-1088, ISSN: 0027-8874

The distributions of Pvu II and Sph I alleles of the N-myc oncogene (also known as MYCN) were studied in a series of normal individuals and pediatric patients with solid tumors. In the case of Pvu II, where the polymorphic site is located 3' of the gene, the frequencies of the allele were 0.27 (11-kilobase fragment) and 0.73 (8-kilobase fragment) in 43 unrelated normal Caucasians. The frequencies of the allele were similar in 40 non-N-myc-amplified neuroblastomas, 47 Wilms' tumors, and 31 other pediatric tumors. In these cases, the genotypes were in Hardy-Weinberg equilibrium. In 18 N-myc-amplified neuroblastomas, however, the observed genotype frequencies deviated from Hardy-Weinberg equilibrium (P less than .005). Similar observations were made with an Sph I restriction fragment length polymorphism where the polymorphic site is located in intron 2. The differences between amplified and nonamplified neuroblastomas suggest a possible involvement of sequences at or near N-myc in the progression of tumors where the N-myc gene is amplified.

Journal article

FARRER LA, BOWCOCK AM, HEBERT JM, BONNETAMIR B, STERNLIEB I, GIAGHEDDU M, STGEORGEHYSLOP P, FRYDMAN M, LOSSNER J, DEMELIA L, CARCASSI C, LEE R, BEKER R, BALE AE, DONISKELLER H, SCHEINBERG IH, CAVALLISFORZA LLet al., 1991, PREDICTIVE TESTING FOR WILSONS-DISEASE USING TIGHTLY LINKED AND FLANKING DNA MARKERS, NEUROLOGY, Vol: 41, Pages: 992-999, ISSN: 0028-3878

Journal article

Kurth JH, Bowcock AM, Erlich HA, Nevo S, Cavalli-Sforza LLet al., 1991, Km typing with PCR: application to population screening., Am J Hum Genet, Vol: 48, Pages: 613-620, ISSN: 0002-9297

The immunoglobulin kappa light chain (IgK) locus may play a significant role in the pathology of both infectious and autoimmune diseases. Most of the work on IgK genetics has been conducted using immunological techniques for allelic typing and sequence analysis. This is restricted by availability of reagents and can be both expensive and time-consuming. PCR primers were designed to amplify the kappa constant gene (Ck), and four allele-specific oligonucleotides (ASOs) were used to distinguish the alleles in the amplified PCR products. Direct sequencing of PCR products was performed to confirm that the primers specifically amplified the Ck region and the ASOs differentiated the Km alleles. Sequencing of an average of 209 nucleotides of DNA from 50 individuals revealed no variation except at codon 191, which is known to be involved in a frequent polymorphism. An analysis of 347 different individual DNAs from 10 human populations was conducted to determine Km allelic frequencies within these populations and to apply this type of data collection to population studies.

Journal article

Bowcock AM, Kidd JR, Mountain JL, Hebert JM, Carotenuto L, Kidd KK, Cavalli-Sforza LLet al., 1991, Drift, admixture, and selection in human evolution: a study with DNA polymorphisms., Proc Natl Acad Sci U S A, Vol: 88, Pages: 839-843, ISSN: 0027-8424

Accuracy of evolutionary analysis of populations within a species requires the testing of a large number of genetic polymorphisms belonging to many loci. We report here a reconstruction of human differentiation based on 100 DNA polymorphisms tested in five populations from four continents. The results agree with earlier conclusions based on other classes of genetic markers but reveal that Europeans do not fit a simple model of independently evolving populations with equal evolutionary rates. Evolutionary models involving early admixture are compatible with the data. Taking one such model into account, we examined through simulation whether random genetic drift alone might explain the variation among gene frequencies across populations and genes. A measure of variation among populations was calculated for each polymorphism, and its distribution for the 100 polymorphisms was compared with that expected for a drift-only hypothesis. At least two-thirds of the polymorphisms appear to be selectively neutral, but there are significant deviations at the two ends of the observed distribution of the measure of variation: a slight excess of polymorphisms with low variation and a greater excess with high variation. This indicates that a few DNA polymorphisms are affected by natural selection, rarely heterotic, and more often disruptive, while most are selectively neutral.

Journal article

Bowcock AM, Herbert JM, 1990, An SspI RFLP at the D13S25 locus identified by the anonymous single copy probe H2-42., Nucleic Acids Res, Vol: 18, ISSN: 0305-1048

Journal article

Hsieh CL, Bowcock AM, Farrer LA, Hebert JM, Huang KN, Cavalli-Sforza LL, Julius D, Francke Uet al., 1990, The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14., Somat Cell Mol Genet, Vol: 16, Pages: 567-574, ISSN: 0740-7750

Serotonin (5-hydroxytryptamine) functions as a neurotransmitter and a hormone. Its diverse actions are mediated by at least seven distinct cell surface receptor subtypes. The serotonin receptor subtype 2 (gene symbol HTR2) is a G-protein-coupled receptor, expressed primarily in the cerebral cortex, where upon stimulation it stimulates the hydrolysis of inositol phospholipids. We have mapped the HTR2 locus to human chromosome 13 and to mouse chromosome 14 by somatic cell hybrid analysis. Linkage studies in CEPH families, using a PvuII RFLP detected with the HTR2 probe, revealed tight linkage between HTR2 and ESD, the locus for esterase D. The most likely position for HTR2 is between ESD and RB1, the retinoblastoma-1 gene. The homologous loci in mouse, Rb-1 and Esd(Es-10) are on mouse chromosome 14, close to ag, agitans, a recessive neurological mutation. Having mapped Htr-2 to mouse chromosome 14, we predict that it falls into this known conserved gene cluster.

Journal article

Bowcock A, Sartorelli V, 1990, Polymorphism and mapping of the IGF1 gene, and absence of association with stature among African Pygmies., Hum Genet, Vol: 85, Pages: 349-354, ISSN: 0340-6717

Probes detecting restriction fragment length polymorphisms (RFLPs) in the insulinlike growth factor (IGF1) gene were isolated and allele frequencies in different human populations determined. No difference was detected between the distribution of IGF1 alleles in Pygmies versus non-Pygmy black Africans, despite the proposal that a defect in the IGF1 gene might be responsible for Pygmy short stature. This was supported by the absence of a correlation of IGF1 genotype with height in the C.A.R. Pygmies. Polymerase chain reaction (PCR) and direct sequencing failed to demonstrate an alteration in the region upstream the IGF1 start site in Pygmies. Linkage analysis demonstrated that IGF1 is tightly linked to the phenylalanine hydroxylase gene on chromosome 12q22-24.1.

Journal article

Stewart EA, Craik CS, Hake L, Bowcock AMet al., 1990, Human carboxypeptidase A identifies a BglII RFLP and maps to 7q31-qter., Am J Hum Genet, Vol: 46, Pages: 795-800, ISSN: 0002-9297

A genomic clone for human carboxypeptidase has been isolated with a probe for rat CPA1 cDNA. A 1.7-kb HindIII/EcoRI fragment from the 3' flanking region of human carboxypeptidase detects a DNA polymorphism with BglIII. Multipoint linkage analysis with an established map of chromosome 7 markers shows that the most likely location of carboxypeptidase is at 7q31-qter, between D7S87 and D7S93. All other placements can be excluded with odds greater than 100:1. These and other markers confirm that carboxypeptidase lies distal to the locus for cystic fibrosis, at a distance of approximately 12 centimorgans. The regions containing identity to the rat gene were sequenced and shown to be 82% identical to exons 9 and 10 of the rat gene. The presence of a codon for isoleucine at the residues corresponding to codon 255 of rat CPA1 cDNA strongly suggests that the A form of human carboxypeptidase has been isolated.

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Bowcock AM, Hall JM, Hebert JM, King MCet al., 1990, Exclusion of the retinoblastoma gene and chromosome 13q as the site of a primary lesion for human breast cancer., Am J Hum Genet, Vol: 46, Pages: 12-17, ISSN: 0002-9297

Chromosome 13q has been suggested as the site of a gene predisposing to human breast cancer, because loss of heterozygosity of alleles on this chromosome has been observed in some ductal breast tumors and because two breast cancer lines are altered at the retinoblastoma gene (RB1) at 13q14. To test this possibility, linkage of breast cancer susceptibility to 14 loci on chromosome 13q loci was assessed in extended families in which breast cancer is apparently inherited as an autosomal dominant trait. RB1 was excluded as the site of a breast cancer gene by a lod score of Z = -7.60 at close linkage for 13 families. Multipoint analysis yielded negative lod scores throughout the region between 13q12 and 13q34; over most of this distance, Z less than -2.0. Therefore, chromosome 13q appears to be excluded as the site of primary lesion for breast cancer in these families. In addition, comparison of tumor versus normal tissues of nonfamilial breast cancer patients revealed an alteration at the 5' end of RB1 in a mucoid carcinoma but no alterations of RB1 in five informative ductal adenocarcinomas. Linkage data and comparisons of tumor and normal tissues suggest that changes in the RBI locus either are secondary alterations associated with progression of some tumors or occur by chance.

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Bowcock AM, Hebert JM, 1989, The anonymous probe pR1-4 which identifies the locus D13S59 detects a BanII RFLP., Nucleic Acids Res, Vol: 17, ISSN: 0305-1048

Journal article

Bowcock AM, Hebert JM, 1989, The anonymous probe pF5A identifying the locus D13S61 detects RFLPs with XmnI and BanII., Nucleic Acids Res, Vol: 17, ISSN: 0305-1048

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Bowcock AM, Hebert JM, Scheffer H, Penninga D, Buys CHet al., 1989, The single copy probe pG24E2.4 [D13S21] reveals a Bsp1286 RFLP at 13q14.1-q14.2., Nucleic Acids Res, Vol: 17, ISSN: 0305-1048

Journal article

Bowcock AM, Hebert JM, Scheffer H, Penninga D, Buys CHet al., 1989, The anonymous probe pG50 identifying the locus D13S24 detects a two allele RFLP with SspI., Nucleic Acids Res, Vol: 17, ISSN: 0305-1048

Journal article

Stewart EA, Kopito R, Bowcock AM, 1989, A PstI polymorphism for the human erythrocyte surface protein band 3 (EPB3) demonstrates close linkage of EPB3 to the nerve growth factor receptor., Genomics, Vol: 5, Pages: 633-635, ISSN: 0888-7543

Erythrocyte surface protein band 3 (EPB3) plays an important role in CO2 transport in the blood. We have isolated a recombinant lambda bacteriophage that contains coding sequence for the human gene. Sequence analysis demonstrated that the human insert contains a portion of exon 13. A 1.1-kb BamHI fragment revealed a two-allele polymorphism with PstI. Alleles of 1.4 and 0.9/0.5 kb were present in Caucasoids at frequencies of 0.74 and 0.26, respectively. EPB3 has previously been mapped to 17q21-qter by in situ hybridization, and linkage analysis showed that EPB3 is tightly linked to the gene for the nerve growth factor receptor (NGFR). The maximum likelihood estimate of recombination (theta) is 0.00, with a lod score of 11.40 and confidence interval of 0.00 to 0.04.

Journal article

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