TY - JOUR
TI - Dating the origin of the CCR5-Delta 32 AIDS-resistance allele by the
coalescence of haplotypes
AU - Stephens, JC
AU - Reich, DE
AU - Goldstein, DB
AU - Shin, HD
AU - Smith, MW
AU - and Carrington, M
AU - Winkler, C
AU - Huttley, GA
AU - Allikmets, R and
AU - Schriml, L
AU - Gerrard, B
AU - Malasky, M
AU - Ramos, MD
AU - Morlot, S and
AU - Tzetis, M
AU - Oddoux, C
AU - di Giovine, FS
AU - Nasioulas, G and
AU - Chandler, D
AU - Aseev, M
AU - Hanson, M
AU - Kalaydjieva, L
AU - Glavac, D
AU - and Gasparini, P
AU - Kanavakis, E
AU - Claustres, M
AU - Kambouris, M and
AU - Ostrer, H
AU - Duff, G
AU - Baranov, V
AU - Sibul, H
AU - Metspalu, A and
AU - Goldman, D
AU - Martin, N
AU - Duffy, D
AU - Schmidtke, J
AU - Estivill, X
AU - and O'Brien, SJ
AU - Dean, M
JO - American Journal of Human Genetics
PY - 1998
VL - 62
TODO - 6
SP - 1507-1515
PB - University of Chicago Press
SN - 0002-9297, 1537-6605
TODO - 10.1086/301867
TODO - null
TODO - The CCR5-Delta 32 deletion obliterates the CCR5 chemokine and the human
immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to
strong resistance against HIV-1 infection and AIDS. A genotype survey of
4,166 individuals revealed a dine of CCR5-Delta 32 allele frequencies of
0%-14% across Eurasia, whereas the variant is absent among native
African, American Indian, and East Asian ethnic groups. Haplotype
analysis of 192 Caucasian chromosomes revealed strong linkage
disequilibrium between CCR5 and two microsatellite loci. By use of
coalescence theory to interpret modern haplotype genealogy, we estimate
the origin of the CCR5-Delta 32-containing ancestral haplotype to be
similar to 700 years ago, with an estimated range of 275-1,875 years.
The geographic dine of CCR5-Delta 32 frequencies and its recent
emergence are consistent with a historic strong selective event (e.g.,
an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its
frequency upward in ancestral Caucasian populations.
ER -