PMID- 9799280
OWN - NLM
STAT- MEDLINE
DCOM- 19990107
LR  - 20210915
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 150
IP  - 3
DP  - 1998 Nov
TI  - Constrained disequilibrium values and hitchhiking in a three-locus system.
PG  - 1295-307
AB  - Positive selection on a new mutant allele can increase the frequencies of closely 
      linked alleles (through hitchhiking), as well as create linkage disequilibrium 
      between them. Because this disequilibrium is induced by the selected allele, one 
      may be able to identify loci under selection by measuring the influence of a 
      candidate locus on pairwise disequilibrium values at nearby loci. The constrained 
      disequilibrium values (CDV) method approaches this problem by examining 
      differences in pairwise disequilibrium values, which have been normalized for 
      two- and three-locus systems, respectively. We have investigated in detail the 
      reliability of inferences based on CDV, using simulation and analytical methods. 
      Our main results are (i) in some circumstances, CDV may not distinguish well 
      between a selected locus and a neighboring neutral locus, but (ii) CDV seldom 
      indicates "selection" in neutral haplotypes with moderate to large 4Nc. We 
      conclude that, although the CDV method does not appear to precisely locate 
      selected alleles, it can be used to screen for regions in which hitchhiking is a 
      plausible hypothesis. We present a microsatellite data set from human chromosome 
      6, in which constrained disequilibrium values suggest the action of selection in 
      a region containing the human leukocyte antigen (HLA)-A and myelin 
      oligodendrocyte glycoprotein (MOG) loci. The connection between hitchhiking and 
      disequilibrium has received relatively little attention, so our investigation 
      presents opportunities to address more general issues.
FAU - Grote, M N
AU  - Grote MN
AD  - Section of Evolution and Ecology, University of California, Davis, California 
      95616, USA. mngrote@ucdavis.edu
FAU - Klitz, W
AU  - Klitz W
FAU - Thomson, G
AU  - Thomson G
LA  - eng
GR  - 5 T32 GM-O7127/GM/NIGMS NIH HHS/United States
GR  - GM-56688/GM/NIGMS NIH HHS/United States
GR  - HD-12731/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
SB  - IM
MH  - *Alleles
MH  - *Computer Simulation
MH  - Gene Frequency
MH  - *Genetic Linkage
MH  - *Genome, Human
MH  - Humans
MH  - *Models, Genetic
MH  - *Models, Theoretical
PMC - PMC1460391
EDAT- 1998/11/03 00:00
MHDA- 1998/11/03 00:01
PMCR- 1999/02/01
CRDT- 1998/11/03 00:00
PHST- 1998/11/03 00:00 [pubmed]
PHST- 1998/11/03 00:01 [medline]
PHST- 1998/11/03 00:00 [entrez]
PHST- 1999/02/01 00:00 [pmc-release]
AID - 10.1093/genetics/150.3.1295 [doi]
PST - ppublish
SO  - Genetics. 1998 Nov;150(3):1295-307. doi: 10.1093/genetics/150.3.1295.