The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel

Abstract

The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze In the last decade, data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database ( http://www.goldenhelix.org/server/israeli ). In the non-Jewish population, up to 1 July 2010, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria and congenital adrenal hyperplasia, as well as data on 195 autosomal recessive diseases among Muslim Israeli Arabs, 11 among the Christian Arabs and 31 among Druze. A single mutation was characterized in 149 out of the 238 rare disorders for which the molecular basis was known. In many diseases, mutation had never been observed in any other population and was present in one family only suggesting that it occurred as a de novo event. In other diseases, the mutation was present in more than one community or even in other populations such as Bedouins from the Arab peninsula or Christians from Lebanon. In the 89 other disorders, more than one mutation was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases such as Bardet Biedl among the Bedouins, the reason may be a selective advantage to the heterozygotes.

Trends in the incidence and causes of severe visual impairment and blindness in children from Israel

“…Consanguineous marriages continue to be prevalent in the Middle East and in the Israeli Arab minority in particular, raising the frequency of autosomal recessive diseases, including RP 24-29 and albinism. 30,31 The prevalence of consanguineous marriages in Israeli Jews declined from 9.7% in 1956 32 to 2.3% in 1991. 25 A significant decrease was also evident in the Israeli Arab population, from 52.9% between 1961 and 1970 to 32.8% in 1991 and 1998 27,33 as well as 35.8% before 2000 to 24% among those married in 2005-2009.…”

Identification of Mutations Causing Inherited Retinal Degenerations in the Israeli and Palestinian Populations Using Homozygosity Mapping

“…Fullfield ERG testing revealed low responses with a cone > rod pattern. Homozygosity mapping performed on five patients revealed many (3)(4)(5)(6)(7)(8)(9)(10)(11) homozygous regions per patient, which contained 9 to 13 candidate genes (Table 1). By combining homozygosity mapping data of family members, a single large shared homozygous region of 14.9 Mb was identified, including RDH12.…”

“…[6][7][8] The Palestinian and Israeli populations include a large number of subpopulations (e.g., Jews, Arab-Muslims, ArabChristians, Bedouin, and Druze) with a relatively high frequency of consanguineous marriages and marriages between members of relatively isolated subpopulations. [9][10][11] The rates of consanguineous marriages are higher among Arab-Muslims, Druze, and Bedouins compared to Christian-Arabs 10 and Jews. 11 In more than 25% of Arab-Muslims and Druze marriages, the Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783 spouses are first cousins, with an additional 20% of the spouses being related in other ways.…”

“…10 Consanguinity is less frequent among Arab-Christians (21% of marriages with first cousins and 11% related), but more frequent among the Bedouin population (35% of marriages with first cousins and 34% related). 9 The Jewish population in Israel consists of a large proportion of immigrants who came to the country during the last half of the 20th century. Until the immigration of these families, many were isolated from other Jewish communities for centuries, and hence were forced to marry their distant or close relatives.…”

Consecutive Mutational Events in a TSHR Allele of Arab Families with Resistance to Thyroid Stimulating Hormone

“…These loss-of-function mutations are found throughout the receptor sequence, without clear localization to hot spots such as CpG regions (24). Whether mutations in the TSHR gene may impart a selective advantage to carrier subjects (6,25) will require more studies to explore this hypothesis.…”