Not all isolates are equal: linkage disequilibrium analysis on Xq13.3 reveals different patterns in Sardinian sub-populations

TY - JOUR

T1 - Not all isolates are equal

T2 - linkage disequilibrium analysis on Xq13.3 reveals different patterns in Sardinian sub-populations

AU - Angius, Andrea

AU - Bebbere, Daniela

AU - Petretto, Enrico

AU - Falchi, Mario

AU - Forabosco, Paola

AU - Maestrale, Battista

AU - Casu, Giuseppina

AU - Persico, Ivana

AU - Melis, Paola M

AU - Pirastu, Mario

PY - 2002/7

Y1 - 2002/7

N2 - Recent studies indicate that, whereas the Sardinian population as a whole is comparable to outbred populations for linkage disequilibrium (LD) mapping of common variants, LD in Sardinian sub-isolates is more extended, making these populations particularly suitable for this approach. To evaluate the extent of LD between microsatellite markers, we compared different sub-populations within Sardinia selected on the basis of their geographical position and isolation: two small isolated villages (Talana, Urzulei), two larger but remote areas (Ogliastra, Nuoro province) and a cohort of samples representing the wider Sardinian population. LD analysis was carried out by using six microsatellite markers that are located on Xq13.3 and that have been extensively studied in different populations. We found different extents and patterns of LD in the sub-population samples depending on their degree of isolation and demographic history. All LD measurements and haplotype analyses indicate that there is a decreasing trend from Talana (the most inbred population, LD up to 9.5-11.5 Mb) to the more outbred Sardinian population (LD only for intervals <2 Mb). In one village (Talana), five haplotype classes accounting for 80% of the entire sample perfectly matched five Ogliastra clusters, supporting the origin of the village from the Ogliastra genetic pool. In contrast, the other village (Urzulei) showed a different pattern of haplotypes with a closer relationship to the Nuoro region sub-population. LD analyses therefore show that even neighbouring isolate villages may differ in their genetic background. Here, we highlight the importance of selecting appropriate populations and/or sub-populations for the analysis of complex traits. Isolated sub-populations showing different extents of LD can provide a powerful method for mapping complex traits by LD scanning at relatively low marker density.

AB - Recent studies indicate that, whereas the Sardinian population as a whole is comparable to outbred populations for linkage disequilibrium (LD) mapping of common variants, LD in Sardinian sub-isolates is more extended, making these populations particularly suitable for this approach. To evaluate the extent of LD between microsatellite markers, we compared different sub-populations within Sardinia selected on the basis of their geographical position and isolation: two small isolated villages (Talana, Urzulei), two larger but remote areas (Ogliastra, Nuoro province) and a cohort of samples representing the wider Sardinian population. LD analysis was carried out by using six microsatellite markers that are located on Xq13.3 and that have been extensively studied in different populations. We found different extents and patterns of LD in the sub-population samples depending on their degree of isolation and demographic history. All LD measurements and haplotype analyses indicate that there is a decreasing trend from Talana (the most inbred population, LD up to 9.5-11.5 Mb) to the more outbred Sardinian population (LD only for intervals <2 Mb). In one village (Talana), five haplotype classes accounting for 80% of the entire sample perfectly matched five Ogliastra clusters, supporting the origin of the village from the Ogliastra genetic pool. In contrast, the other village (Urzulei) showed a different pattern of haplotypes with a closer relationship to the Nuoro region sub-population. LD analyses therefore show that even neighbouring isolate villages may differ in their genetic background. Here, we highlight the importance of selecting appropriate populations and/or sub-populations for the analysis of complex traits. Isolated sub-populations showing different extents of LD can provide a powerful method for mapping complex traits by LD scanning at relatively low marker density.

KW - Chromosome Mapping

KW - DNA

KW - Demography

KW - Gene Frequency

KW - Genetic Markers

KW - Genetic Variation

KW - Genetics, Population

KW - Haplotypes

KW - Humans

KW - Italy

KW - Linkage Disequilibrium

KW - Male

KW - Microsatellite Repeats

KW - Models, Genetic

KW - Selection, Genetic

KW - X Chromosome

U2 - 10.1007/s00439-002-0753-z

DO - 10.1007/s00439-002-0753-z

M3 - Article

C2 - 12136230

SN - 0340-6717

VL - 111

SP - 9

EP - 15

JO - Human Genetics

JF - Human Genetics

IS - 1

ER -