Abstract:
:ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive survey of sequence variation in ATM in diverse human populations. The protein-encoding exons of the gene (9,168 bp) and the adjacent intron and untranslated sequences (14,661 bp) were analyzed in 93 individuals from seven major human populations. In addition, the coding sequence was analyzed in one chimpanzee, one gorilla, one orangutan, and one Old World monkey. In human ATM, 88 variant sites were discovered by denaturing high-performance liquid chromatography, which is 96%-100% sensitive for detection of DNA sequence variation. ATM was compared to 14 other autosomal genes for nucleotide diversity. The noncoding regions of ATM had diversity values comparable to other genes, but the coding regions had very low diversity, especially in the last 29% of the protein sequence. A test of the neutral evolution hypothesis, through use of the Hudson/Kreitman/Aguadé statistic, revealed that this region of the human ATM gene was significantly constrained relative to that of the orangutan, the Old World monkey, and the mouse, but not relative to that of the chimpanzee or the gorilla. ATM displayed extensive linkage disequilibrium, consistent with suppression of meiotic recombination at this locus. Seven haplotypes were defined. Two haplotypes accounted for 82% of all chromosomes analyzed in all major populations; two others carrying the same D126E missense polymorphism accounted for 33% of chromosomes in Africa but were never observed outside of Africa. The high frequency of this polymorphism may be due either to a population expansion within Africa or to selective pressure.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Thorstenson YR,Shen P,Tusher VG,Wayne TL,Davis RW,Chu G,Oefner PJdoi
10.1086/321296subject
Has Abstractpub_date
2001-08-01 00:00:00pages
396-412issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(07)61085-4journal_volume
69pub_type
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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pub_type: 杂志文章
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
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journal_title:American journal of human genetics
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doi:
更新日期:1991-05-01 00:00:00
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journal_title:American journal of human genetics
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doi:
更新日期:1991-10-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301948
更新日期:1998-08-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302379
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 临床试验,杂志文章
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2007.12.011
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:1979-07-01 00:00:00
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pub_type: 杂志文章
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journal_title:American journal of human genetics
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pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
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