PMID- 12073008
OWN - NLM
STAT- MEDLINE
DCOM- 20020808
LR  - 20061115
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 110
IP  - 5
DP  - 2002 May
TI  - Estimation of single nucleotide polymorphism allele frequency in DNA pools by 
      using Pyrosequencing.
PG  - 395-401
AB  - Positional cloning of genes underlying complex diseases, such as type 2 diabetes 
      mellitus (T2DM), typically follows a two-tiered process in which a chromosomal 
      region is first identified by genome-wide linkage scanning, followed by 
      association analyses using densely spaced single nucleotide polymorphic markers 
      to identify the causal variant(s). The success of genome-wide single nucleotide 
      polymorphism (SNP) detection has resulted in a vast number of potential markers 
      available for use in the construction of such dense SNP maps. However, the cost 
      of genotyping large numbers of SNPs in appropriately sized samples is nearly 
      prohibitive. We have explored pooled DNA genotyping as a means of identifying 
      differences in allele frequency between pools of individuals with T2DM and 
      unaffected controls by using Pyrosequencing technology. We found that allele 
      frequencies in pooled DNA were strongly correlated with those in individuals 
      (r=0.99, P<0.0001) across a wide range of allele frequencies (0.02-0.50). We 
      further investigated the sensitivity of this method to detect allele frequency 
      differences between contrived pools, also over a wide range of allele 
      frequencies. We found that Pyrosequencing was able to detect an allele frequency 
      difference of less than 2% between pools, indicating that this method may be 
      sensitive enough for use in association studies involving complex diseases where 
      a small difference in allele frequency between cases and controls is expected.
FAU - Gruber, Jonathan D
AU  - Gruber JD
AD  - Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical 
      Research Branch, National Institute of Diabetes and Digestive and Kidney 
      Diseases/NIH, 4212 North 16th Street, Phoenix, AZ 85016, USA.
FAU - Colligan, Peter B
AU  - Colligan PB
FAU - Wolford, Johanna K
AU  - Wolford JK
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020409
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - DNA/*genetics/*isolation & purification
MH  - Diabetes Mellitus/genetics
MH  - Female
MH  - Gene Frequency/*genetics
MH  - Humans
MH  - Indians, North American/genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Sequence Analysis, DNA/*methods
EDAT- 2002/06/20 10:00
MHDA- 2002/08/09 10:01
CRDT- 2002/06/20 10:00
PHST- 2002/02/01 00:00 [received]
PHST- 2002/03/04 00:00 [accepted]
PHST- 2002/06/20 10:00 [pubmed]
PHST- 2002/08/09 10:01 [medline]
PHST- 2002/06/20 10:00 [entrez]
AID - 10.1007/s00439-002-0722-6 [doi]
PST - ppublish
SO  - Hum Genet. 2002 May;110(5):395-401. doi: 10.1007/s00439-002-0722-6. Epub 2002 Apr 
      9.