Author
Tara K. Cox
Other affiliations: Johns Hopkins University School of Medicine
Bio: Tara K. Cox is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Chromosome 21 & Genetic linkage. The author has an hindex of 6, co-authored 8 publications receiving 3839 citations. Previous affiliations of Tara K. Cox include Johns Hopkins University School of Medicine.
Papers
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TL;DR: Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations.
Abstract: Approximately 70 percent of the mutations in cystic fibrosis patients correspond to a specific deletion of three base pairs, which results in the loss of a phenylalanine residue at amino acid position 508 of the putative product of the cystic fibrosis gene. Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations. A small set of these latter mutant alleles (about 8 percent) may confer residual pancreatic exocrine function in a subgroup of patients who are pancreatic sufficient. The ability to detect mutations in the cystic fibrosis gene at the DNA level has important implications for genetic diagnosis.
3,816 citations
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TL;DR: A comparative study of cytogenetic heteromorphisms and seven PCR-based DNA polymorphisms for detecting the origin of the additional chromosome 21 in 68 cases of Down syndrome raised the possibility of recombination between the two marker systems, particularly on the short arm.
Abstract: Nondisjunction in trisomy 21 has traditionally been studied by cytogenetic heteromorphisms. Those studies assumed no crossing-over on the short arm of chromosome 21. Recently, increased accuracy of detection of the origin of nondisjunction has been demonstrated by DNA polymorphism analysis. We describe a comparative study of cytogenetic heteromorphisms and seven PCR-based DNA polymorphisms for detecting the origin of the additional chromosome 21 in 68 cases of Down syndrome. The polymorphisms studied were the highly informative microsatellites at loci D21S215, D21S120, D21S192, IFNAR, D21S156, HMG14, and D21S171. The meiotic stage of nondisjunction was assigned on the basis of the pericentromeric markers D21S215, D21S120, and D21S192. Only unequivocal cytogenetic results were compared with the results of the DNA analysis. The parental and meiotic division origin could be determined in 51% of the cases by using the cytogenetic markers and in 88% of the cases by using the DNA markers. Although there were no discrepancies between the two scoring systems regarding parental origin, there were eight discrepancies regarding meiotic stage of nondisjunction. Our results raise the possibility of recombination between the two marker systems, particularly on the short arm.
58 citations
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TL;DR: A polymorphism due to a T-to-C substitution at nucleotide 549 of the 3′UT region with heterozygosity of 46% has been identified and is placed in the linkage map of human chromosome 21.
Abstract: We used single-strand conformation polymorphism (SSCP) to detect DNA polymorphisms in the 3′ untranslated (3′UT) region of the gene for cystathionine β-synthase (CBS). A polymorphism due to a T-to-C substitution at nucleotide 549 of the 3′UT region with heterozygosity of 46% has been identified. Genotypes for this polymorphism have been obtained in all of the informative CEPH families, and CBS has been placed in the linkage map of human chromosome 21.
19 citations
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TL;DR: A plasmid, AWZ1, that contained a dinucleotide (GT)n repeat was identified from a chromosome 21-specific genomic library and is the closest polymorphic marker to alphoid sequences on this chromosome.
13 citations
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TL;DR: A highly polymorphic (GT)n repeat with 14 alleles that is closely linked to the amyloid precursor protein (APP) gene on human chromosome 21 will be useful for studies of linkage of disorders such as Alzheimer disease to the APP gene.
Abstract: We describe a highly polymorphic (GT)n repeat with 14 alleles that is closely linked to the amyloid precursor protein (APP) gene on human chromosome 21. This marker, D21S210, will be useful for studies of linkage of disorders such as Alzheimer disease to the APP gene.
10 citations
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TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
Abstract: Overlapping complementary DNA clones were isolated from epithelial cell libraries with a genomic DNA segment containing a portion of the putative cystic fibrosis (CF) locus, which is on chromosome 7 Transcripts, approximately 6500 nucleotides in size, were detectable in the tissues affected in patients with CF The predicted protein consists of two similar motifs, each with (i) a domain having properties consistent with membrane association and (ii) a domain believed to be involved in ATP (adenosine triphosphate) binding A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients
6,731 citations
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Baylor College of Medicine1, Chinese Academy of Sciences2, Chinese National Human Genome Center3, University of Hong Kong4, The Chinese University of Hong Kong5, Hong Kong University of Science and Technology6, Illumina7, McGill University8, Washington University in St. Louis9, University of California, San Francisco10, Wellcome Trust Sanger Institute11, Beijing Normal University12, Health Sciences University of Hokkaido13, Shinshu University14, University of Tsukuba15, Howard University16, University of Ibadan17, Case Western Reserve University18, University of Utah19, Cold Spring Harbor Laboratory20, Johns Hopkins University21, University of Oxford22, North Carolina State University23, National Institutes of Health24, Massachusetts Institute of Technology25, Chinese Academy of Social Sciences26, Kyoto University27, Nagasaki University28, Wellcome Trust29, Genome Canada30, Foundation for the National Institutes of Health31, University of Maryland, Baltimore32, Vanderbilt University33, Stanford University34, New York University35, University of California, Berkeley36, University of Oklahoma37, University of New Mexico38, Université de Montréal39, University of California, Los Angeles40, University of Michigan41, University of Wisconsin-Madison42, London School of Economics and Political Science43, Genetic Alliance44, GlaxoSmithKline45, University of Washington46, Harvard University47, University of Chicago48, Fred Hutchinson Cancer Research Center49, University of Tokyo50
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Abstract: The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.
5,926 citations
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TL;DR: It is shown that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed.
Abstract: Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease.
5,634 citations
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27 Oct 2005
TL;DR: A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.
5,479 citations
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TL;DR: A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein.
Abstract: Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.
4,110 citations