PMID- 10391210
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20081121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 3
DP  - 1999 Jul
TI  - Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure
      homeostasis.
PG  - 239-47
AB  - Sequence variation in human genes is largely confined to single-nucleotide
      polymorphisms (SNPs) and is valuable in tests of association with common diseases
      and pharmacogenetic traits. We performed a systematic and comprehensive survey of
      molecular variation to assess the nature, pattern and frequency of SNPs in 75
      candidate human genes for blood-pressure homeostasis and hypertension. We assayed
      28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3'
      untranslated regions (UTRs), introns and coding sequence of these genes, for
      sequence differences in individuals of African and Northern European descent
      using high-density variant detection arrays (VDAs). We identified 874 candidate
      human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy
      rate of 21% for VDA detection. The SNPs detected have an average minor allele
      frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs,
      54% lead to a predicted change in the protein sequence, implying a high level of 
      human protein diversity. These protein-altering SNPs are 38% of the total number 
      of such SNPs expected, are more likely to be population-specific and are rarer in
      the human population, directly demonstrating the effects of natural selection on 
      human genes. Overall, the degree of nucleotide polymorphism across these human
      genes, and orthologous great ape sequences, is highly variable and is correlated 
      with the effects of functional conservation on gene sequences.
FAU - Halushka, M K
AU  - Halushka MK
AD  - Department of Genetics and Center for Human Genetics, Case Western Reserve
      University School of Medicine and University Hospitals of Cleveland, Ohio 44106, 
      USA.
FAU - Fan, J B
AU  - Fan JB
FAU - Bentley, K
AU  - Bentley K
FAU - Hsie, L
AU  - Hsie L
FAU - Shen, N
AU  - Shen N
FAU - Weder, A
AU  - Weder A
FAU - Cooper, R
AU  - Cooper R
FAU - Lipshutz, R
AU  - Lipshutz R
FAU - Chakravarti, A
AU  - Chakravarti A
LA  - eng
GR  - R01 HG01847/HG/NHGRI NIH HHS/United States
GR  - U10 HL54466/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (3' Untranslated Regions)
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - 3' Untranslated Regions
MH  - 5' Untranslated Regions
MH  - Alleles
MH  - Animals
MH  - Base Sequence
MH  - Blood Pressure/*genetics
MH  - DNA/genetics
MH  - Evolution, Molecular
MH  - Gene Frequency
MH  - Genetic Variation
MH  - Homeostasis/genetics
MH  - Humans
MH  - Hypertension/genetics
MH  - Pan troglodytes/genetics
MH  - *Polymorphism, Genetic
MH  - Proteins/genetics
MH  - Sequence Homology, Nucleic Acid
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/10297 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jul;22(3):239-47. doi: 10.1038/10297.