A putative gene located at the MHC class I region around the D6S105 marker contributes to the setting of CD8+ T-lymphocyte numbers in humans.
Significant associations between human leucocyte antigen (HLA)-A and -B alleles and CD8+ T-lymphocyte numbers have been reported in the literature in both healthy populations and in HFE-haemochromatosis patients. In order to address whether HLA alleles themselves or alleles at linked genes are responsible for these associations, several genetic markers at the MHC class I region were typed on a population of 147 apparently healthy unrelated subjects phenotypically characterized for their CD8+ and CD4+ T-lymphocyte numbers. By using a machine learning approach, a set of rules was generated that predict the number of CD8+ T-lymphocyte numbers on the basis of the information of the D6S105 microsatellite alleles only. We demonstrate that the previously reported associations with HLA-A and -B alleles are due to the presence of common long (up to 4 megabases long) haplotypes that increased in frequency recently due to positive selection and that encompass a region where a putative gene contributing to the setting of CD8+ T lymphocytes is located, in the neighbourhood of microsatellite locus D6S105, in the 6p21.3 region.
Vieira
J
J
Molecular Evolution, Instituto de Biologia Molecular e Celular, Porto, Portugal. jbvieira@ibmc.up.pt
Cardoso
C S
CS
Pinto
J
J
Patil
K
K
Brazdil
P
P
Cruz
E
E
Mascarenhas
C
C
Lacerda
R
R
Gartner
A
A
Almeida
S
S
Alves
H
H
Porto
G
G
D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005805:Genes, MHC Class I / Q000235:genetics*; D005819:Genetic Markers; D015234:HLA-A Antigens / Q000235:genetics; D015788:HLA-A1 Antigen; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D018655:Lymphocyte Count; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics
D005819:Genetic Markers; C103673:HFE protein, human; D015234:HLA-A Antigens; D015788:HLA-A1 Antigen; C035524:HLA-A29 antigen; D015235:HLA-B Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins