Fine mapping of a putative tuberculosis-susceptibility locus on chromosome 15q11-13 in African families.
Host genetics plays an important role in individual susceptibility and resistance to infectious diseases, but no genes have yet been identified using genome-wide screens. Twin studies have indicated that tuberculosis susceptibility has a significant host genetic component, and several genes appear to be involved. Recently, a genome-wide linkage analysis of 136 African families identified chromosome 15q11-13 as a region with suggestive evidence of linkage, with a LOD score of 2.0. We tested 10 microsatellite markers and 5 positional candidate genes in this chromosomal region for deviation from random transmission from parents to affected offspring. The polymorphisms, lying in a region of 14 cM, were initially typed in the same 79 Gambian families used in the genome screen. A borderline significant association with a 7 bp deletion in UBE3A (P = 0.01) was found. This polymorphism was then evaluated further in a larger series of families with tuberculosis, including 44 Guinean families and 57 families from South Africa. Testing for association between the deletion and tuberculosis across all the families using the exact symmetry test further supported the association (overall P = 0.002). These fine-mapping data suggest that UBE3A or a closely flanking gene may be a tuberculosis-susceptibility locus.
Cervino
Alessandra C L
AC
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Lakiss
Said
S
Sow
Oumou
O
Bellamy
Richard
R
Beyers
Nulda
N
Hoal-van Helden
Eileen
E
van Helden
Paul
P
McAdam
Keith P W J
KP
Hill
Adrian V S
AV
D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D005190:Family; D005260:Female; D005714:Gambia; D020022:Genetic Predisposition to Disease; D016701:Guinea; D006579:Heterozygote; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013019:South Africa; D014376:Tuberculosis / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D011994:Recombinant Proteins; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases