HGM 2011 - Dubai, UAE


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Ghazi Tadmouri - Abstract

Ghazi O. Tadmouri


Title: Genetic Disorders in Arabs from Clinical Genetics to Human Genome Variability

 

Arabs are a panethnicity of peoples of various ancestral origins, religious backgrounds, and historic identities. They originate from the region including Mesopotamia, the Levant, the Arabian Peninsula, and North Africa. The Arab World is the largest geocultural unit in the world after Russia and Anglo-America, with a population exceeding 360 million and spanning more than 14 million square kilometers. According to the Recent Out-of-Africa model describing the origin of modern humans, the region has repeatedly served as a migratory passageway between Africa and Eurasia and has acted as an incubator for the early diversification of non-African lineages. This diversity reflects today with the presence of 955 genetic disease entities among Arabs according to the CTGA Database. This diversity also echoes at the clinical level as observed in the large number of disease groups, affected systems, incidence rates, geographical distributions, clinical subtypes, and disease phenotypes. This latter characteristic is further amplified by the presence of comorbidity in patients from the region with combinations of major disorders including hemoglobinopathies, cystic fibrosis, Down syndrome, G6PD deficiency, and many others.

on the other hand, nearly two-third (61%) of genetic disorders in Arabs follow an autosomal recessive mode of inheritance and this is highly attributed to the widespread practice of consanguineous marriages in the region. Certainly, the availability of many consanguineous and extended families in the region has fueled the process of gene identification for various inherited disorders, thus, providing invaluable resources for gene annotation and human genome variation.

Recently, the Centre for Arab Genomic Studies initiated a long-term Arab Human Variome Project to document human genome variation in the region with geographically-oriented and disease-oriented perspectives. In a striking example of the spatial distribution of diversity, the State of Qatar, one of the smallest Arab countries in terms of area and population size, exhibited at least 12 novel mutations in 11 different loci. From a disease perspective, two main examples may be noted. (1) The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene demonstrates a heterogeneous profile in a small region including the neighboring countries of Bahrain, Qatar, the United Arab Emirates, and Oman. In brief, the 2043delG (c.1911delG) mutations is the most common in Bahrain, while c.3700A>G (p.I1234V) is the most common in Qatar, and the c.1647T>G (p.S549R) mutation is commonly observed in Oman and the UAE. (2) ?-Thalassemia exhibits another extreme example of diversity with at least 73 ?-globin mutations leading to the disease in Arab populations.

At present, 36% of reported genetic disorders in Arabs remain confined to clinical observations. Efforts to decipher their molecular pathologies will definitely result in high value knowledge base. The organization of such information will have direct implications on genetic counseling, prenatal diagnosis, genotype-to-phenotype correlations, evaluation of individual prognosis, and appropriate patient management.

   
 

   
   
   
   

Sheikh Hamdan Bin Rashid Al Maktoum
Award for Medical Science

 



Human Genome Organisation

Centre for Arab Genomic Studies

 
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