TY - JOUR
T1 - The natural history of an HLA haplotype and its recombinants
AU - D'Alfonso, Sandra
AU - Borelli, Iolanda
AU - Dall'Omo, Annamaria
AU - Bolognesi, Elisabetta
AU - Partanen, Jukka
AU - Levo, Antti
AU - Pociot, Flemming
AU - Fan, Lian
AU - Juji, Takeo
AU - Hammond, Michael
AU - Tosi, Roberto
AU - Richiardi, Patricia Momigliano
N1 - Funding Information:
AcknowledgmentsmThis work was supported by MURST 60%. Eli-sabetta Bolognesi is a fellow of “Gruppo di Cooperazione in Cancer-ologia”, Turin, Italy.
PY - 1998
Y1 - 1998
N2 - The presence of haplotype-specific recombination sites can be determined by analyzing the conservation of extended haplotypes in the population. This approach considers all meioses in the history of the population and requires the presence of characteristic markers that easily allow the identification of the haplotype or of its recombined segments. The recombination breakpoint can then be mapped by looking for shared alleles between haplotypes selected through the specific marker/s. We identified a rare perfect tandem duplication of a 145 base pair segment in the LTA promoter, which tags a B60 (B60D) haplotype. The duplication was detected in 16/90 B60+ Europeans, while absent in 101 B60+ Orientals. The conservation of the class I end and the extreme variability of the class II end suggested that the present-day B60D haplotypes originated from an ancestral haplotype by recombination events centromeric to the duplicated sequence. Through a fine mapping using markers of the HLA central region a preferential recombination site was localized in the 60 kilobase interval between TNFd,e, and D6S273/K11 Amicrosatellite loci (i.e., between LST1 and BAT3 genes). This site behaves as a potent recombination enhancer leading to fragmentation in most of the extant B60D haplotypes and can be considered responsible for their 'instability'. In the relatively recently founded Finnish population, where the LST1/BAT3 interval recombination has probably not yet had the chance to occur, a founder effect can explain the presence of a rare DP (DPB1(*)1601) allele in most B60D haplotypes in this population.
AB - The presence of haplotype-specific recombination sites can be determined by analyzing the conservation of extended haplotypes in the population. This approach considers all meioses in the history of the population and requires the presence of characteristic markers that easily allow the identification of the haplotype or of its recombined segments. The recombination breakpoint can then be mapped by looking for shared alleles between haplotypes selected through the specific marker/s. We identified a rare perfect tandem duplication of a 145 base pair segment in the LTA promoter, which tags a B60 (B60D) haplotype. The duplication was detected in 16/90 B60+ Europeans, while absent in 101 B60+ Orientals. The conservation of the class I end and the extreme variability of the class II end suggested that the present-day B60D haplotypes originated from an ancestral haplotype by recombination events centromeric to the duplicated sequence. Through a fine mapping using markers of the HLA central region a preferential recombination site was localized in the 60 kilobase interval between TNFd,e, and D6S273/K11 Amicrosatellite loci (i.e., between LST1 and BAT3 genes). This site behaves as a potent recombination enhancer leading to fragmentation in most of the extant B60D haplotypes and can be considered responsible for their 'instability'. In the relatively recently founded Finnish population, where the LST1/BAT3 interval recombination has probably not yet had the chance to occur, a founder effect can explain the presence of a rare DP (DPB1(*)1601) allele in most B60D haplotypes in this population.
KW - Central HLA region
KW - HLA extended haplotype
KW - HLA population genetics
KW - Haplospecific markers
KW - Preferential recombination site
UR - http://www.scopus.com/inward/record.url?scp=7144254469&partnerID=8YFLogxK
U2 - 10.1007/s002510050394
DO - 10.1007/s002510050394
M3 - Article
SN - 0093-7711
VL - 48
SP - 8
EP - 15
JO - Immunogenetics
JF - Immunogenetics
IS - 1
ER -