title: Dissecting the genetic make-up of North-East Sardinia using a large set of haploid and autosomal markers.
abstract: Sardinia has been used for genetic studies because of its historical isolation, genetic homogeneity and increased prevalence of certain rare diseases. Controversy remains concerning the genetic substructure and the extent of genetic homogeneity, which has implications for the design of genome-wide association studies (GWAS). We revisited this issue by examining the genetic make-up of a sample from North-East Sardinia using a dense set of autosomal, Y chromosome and mitochondrial markers to assess the potential of the sample for GWAS and fine mapping studies. We genotyped individuals for 500K single-nucleotide polymorphisms, Y chromosome markers and sequenced the mitochondrial hypervariable (HVI-HVII) regions. We identified major haplogroups and compared these with other populations. We estimated linkage disequilibrium (LD) and haplotype diversity across autosomal markers, and compared these with other populations. Our results show that within Sardinia there is no major population substructure and thus it can be considered a genetically homogenous population. We did not find substantial differences in the extent of LD in Sardinians compared with other populations. However, we showed that at least 9% of genomic regions in Sardinians differed in LD structure, which is helpful for identifying functional variants using fine mapping. We concluded that Sardinia is a powerful setting for genetic studies including GWAS and other mapping approaches.
authors.affiliation: Department of Clinical Genetics, Medical Genomics, Free University Medical Center, Amsterdam, The Netherlands.
authors.forename: Luba M
authors.initials: LM
authors.lastname: Pardo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piras
authors.forename: Rosanna
authors.initials: R
authors.lastname: Asproni
authors.forename: Kristiaan J
authors.initials: KJ
authors.lastname: van der Gaag
authors.forename: Attilio
authors.initials: A
authors.lastname: Gabbas
authors.forename: Andres
authors.initials: A
authors.lastname: Ruiz-Linares
authors.forename: Peter
authors.initials: P
authors.lastname: de Knijff
authors.forename: Maria
authors.initials: M
authors.lastname: Monne
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rizzu
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
mesh_terms: D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005819:Genetic Markers; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006238:Haploidy; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008928:Mitochondria / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers