A Pst+ polymorphism in the HEXA gene with an unusual geographic distribution.
A polymorphic variant in the human HEXA gene is described. This gene encodes the alpha-subunit of hexosaminidase A, the enzyme which is deficient in Tay-Sachs disease (TSD). In individuals carrying the polymorphism there is a T-->C transition at position -6 in intron 13. The substitution creates a site for the restriction endonuclease Pst1. This variant has an unusual ethnogeographic distribution. It occurs on 1.4% of non-TSD carrier chromosomes in Ashkenazi Jews. All individuals ascertained carrying the Pst+ allele have ancestry in Lithuania, Belarus and Ukraine. By contrast, no individuals carrying the Pst+ allele have been detected among non-Jewish Lithuanians, Jews of Sephardic origin or in several other ethnic groups. Two unrelated non-Jewish families have been identified in which the Pst+ variant occurs. In both cases the variant occurs on a chromosome carrying a novel TSD mutation (G772C) association with the B1 phenotype. The Pst+ G772C chromosomes are of Scots-Irish descent.
Kaplan
F
F
Department of Biochemical Genetics, McGill University, Montreal Children's Hospital Research Institute, Quebec, Canada.
Kapoor
S
S
Lee
D
D
Fernandes
M
M
Vienozinskis
M
M
Mascisch
A
A
Scriver
C R
CR
Lim-Steele
J
J
Kaback
M
M
Zeiger
K
K
Zoossman-Diskin
A
A
Bonne-Tamir
B
B
Landels
E
E
Bobrow
M
M
Hechtman
P
P
D000483:Alleles; D001483:Base Sequence; D015252:Deoxyribonucleases, Type II Site-Specific; D054818:Hexosaminidase A; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013661:Tay-Sachs Disease / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases