With the remarkable advances in the field of medical genetics over the past 50 years, consanguinity has become a source of major scientific and public interest worldwide. Consanguinity is defined as marriage between individuals who are second cousins or more closely related. However, lesser degrees of consanguinity, which are relevant to pregnancy outcomes, have been documented, especially in highly inbred families and tribes. Although it is not a favored religious practice, consanguinity is commonplace (20% to 70% of marriages) in the Middle East. It is deeply rooted in the Arabic culture and has been practiced over many generations not only by Muslims, but also by Christian Arabs. Factors that promote consanguinity in these societies include economic reasons, revolving aroundthe preservation of wealth, psychosocial advantages, and geographical and tribal traditions. Despite their perceived social advantages, consanguineous marriages are associated with a higher frequency of autosomal recessive disorders and multifactorial birth defects. These translate into excess prenatal, perinatal, and postnatal mortality. There is no clear association between parental consanguinity and the frequency of common diseases such as diabetes mellitus, asthma, or adult-onset behavioral and psychiatric disorders. One of the scientifically useful features of consanguinity is that it facilitates homozygosity mapping of disease related genes. Homozygosity mapping in inbred families or isolated populations is a practical strategy for mapping the genes responsible for rare autosomal recessive disorders. The high prevalence of consanguinity in our populations, as well as the large average family size, make it possible to identify inbred families with rare recessive disorders that are large enough to independently establish linkage. In these families, individuals with rare recessive traits are likely to have inherited both copies of the mutated gene from a common ancestor, and are thus identical by descent not only at the trait locus but also at neighboring marker loci. Homozygosity mapping overcomes two major obstacles to gene discovery, locus heterogeneity and variable expressivity. The successful mapping of genes can be used to develop diagnostic tests for carrier identification and for prenatal or preimplantation diagnosis. The identification of the genes after mapping leads to the development of more specific diagnostic tools. The Shafallah Medical Genetics Center has taken advantage of the prevalent consanguinity in our populations, the advances in genotyping and sequencing technology and the robust available analytic tools to initiate gene discovery projects for complex disorders such as epilepsy and autism spectrum disorders. In addition, gene mapping and identification of rare autosomal recessive disorders is an ongoing effort in the center. Collaboration with other teams from Arabic countries has lead to the mapping of five rare autosomal recessive disorder genes. Gene identification by Sanger and Next Generation sequencing is currently ongoing for these five disorders.

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