title: Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian Community Through Genomic Runs of Homozygosity.
abstract: Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes that record populations' mating patterns in the past. We performed microarray genotyping on 15 individuals from a small isolated Tunisian community. We estimated the individual and population genome-wide level of homozygosity from data on ROH above 0.5 Mb in length. We found a high average number of ROH per individual (48.2). The smallest ROH category (0.5-1.49 Mb) represents 0.93% of the whole genome, while medium-size (1.5-4.99 Mb) and long-size ROH (≥5 Mb) cover 1.18% and 0.95%, respectively. We found that genealogical individual inbreeding coefficients (Fped ) based on three- to four-generation pedigrees are not reliable indicators of the current proportion of genome-wide homozygosity inferred from ROH (FROH ) either for 0.5 or 1.5 Mb ROH length thresholds, while identity-by-descent sharing is a function of shared coancestry. This study emphasizes the effect of reproductive isolation and a prolonged practice of consanguinity that limits the genetic heterogeneity. It also provides evidence of both recent and ancient parental relatedness contribution to the current level of genome-wide homozygosity in the studied population. These findings may be useful for evaluation of long-term effects of inbreeding on human health and for future applications of ROHs in identifying recessive susceptibility genes.
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Nizar
authors.initials: N
authors.lastname: Ben Halim
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Majdi
authors.initials: M
authors.lastname: Nagara
authors.affiliation: Eukaryote Genotyping Platform, Institut Pasteur, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Regnault
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Sana
authors.initials: S
authors.lastname: Hsouna
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Lasram
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Hela
authors.initials: H
authors.lastname: Azaiez
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Laroussi
authors.initials: L
authors.lastname: Khemira
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Rachid
authors.initials: R
authors.lastname: Saidane
authors.affiliation: Clinical Biochemistry Laboratory, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Slim Ben
authors.initials: SB
authors.lastname: Ammar
authors.affiliation: ENT Department, la Rabta Hospital, Tunis, Tunisia.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Besbes
authors.affiliation: Inserm UMRS587, Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris Cedex 15, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.affiliation: Inserm UMRS587, Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris Cedex 15, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Laboratory of Biomedical Genomics and Oncogenetics, Pasteur Institute of Tunis, Tunis, Le Belvédère, Tunisia.
authors.forename: Lilia
authors.initials: L
authors.lastname: Romdhane
mesh_terms: D003241:Consanguinity; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D060047:Reproductive Isolation; D017422:Sequence Analysis, DNA; D014416:Tunisia
keywords: Tunisia; genealogy; human isolate; identity-by-descent; inbreeding; run of homozygosity