Genetic history of the Arab world

Genetic history of the Arab world refers to the analyses of the genetics of ethnic Arab populations within the Middle East and North Africa. The Arab world has one of the highest rates of genetic disorders globally; some 906 pathologies are endemic to the Arab states, including thalassaemia, Tourette's syndrome, Wilson's disease, Charcot-Marie-Tooth disease, mitochondrial encephalomyopathies, and Niemann-Pick disease.[1]

## Databases[edit]

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Several organizations maintain genetic databases for each Arabic country, such as Saudi Human Genome Program (SHGP) but Even though the KGP, SHGP, QGP, BGP and EGP are revisiting the genetics and genomics of Arab populations’ ancestries, lack of complete coordination between the initiatives is a major limitation on revealing the real disease markers of the Arab population.[2]

The Centre for Arab Genomic Studies (CAGS) is the main organization based in the United Arab Emirates. It initiated a pilot project to construct the Catalogue for Transmission Genetics in Arabs (CTGA) database for genetic disorders in Arab populations. At present, the CTGA database is centrally maintained in Dubai, and hosts entries for nearly 1540 Mendelian disorders and related genes. This number is increasing as researchers are joining the largest Arab scientific effort to define genetic disorders described in the region. The Center promotes research studies on these emergent disorders.[3] Some of the genetic disorders endemic to the Arab world are: hemoglobinopathy, sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency, and fragile X syndrome (FXS), which is an inherited genetic condition with critical consequences. The Centre provide information about specific countries,[4] and maintain a list of Genomic diseases.[5][6][7]

Specific rare autosomal recessive diseases are high in Arabic countries like Bardet Biedl syndrome, Meckel syndrome, congenital chloride diarrhea, severe childhood autosomal recessive muscular dystrophy (SMARMD) lysosomal storage diseases and PKU are high in the Gulf states. Dr Teebi's book provides detailed information and by country.[8] Even the Middle East respiratory syndrome coronavirus (MERS-CoV) that was first identified in Saudi Arabia last year, it has infected 77 people, mostly in the Middle East and Europe. Forty of them – more than half – have died. But MERS is not yet a pandemic, could become pervasive in genetic disease patient. [9]

Dr Thurman' guidebook about Rare genetic diseases[10] Another book Arabic genetic disorders layman guide[11] Saudi Journal article about genetic diseases in Arabic countries[12] The highest proportion of genetic disorders manifestations are: congenital malformations followed by endocrine metabolic disorders and then by neuron disorders (such as Neuromotor disease)and then by blood immune disorders and then neoplasms. The Mode of Inheritance is mainly autosomal recessive followed by autosomal dominant. Some of the diseases are beta-thalassemia mutations, sickle-cell disease, congenital heart-disease, glucose-6-phosphate dehydrogenase deficiency, alpha-thalassemia, molecular characterization, recessive osteoperosis, gluthanione-reducatsafe DEf. A study about sickle cell anemia in Arabs[13] article about Birth defects[14] Glucose phosphate isomerase deficiency responsible for unexpected hemolytic episodes.[15] one of late Dr Teebi's syndromes.[16] flash cards guide.[17][18][19][20] NY Times article[21] In Palestinian Arabs study[22] study about potential on pharmacology [23] another study on Arab Palestinians[24] Database of Genetic disorders in Arabs study[25] In Palestinians[26] new general study about databases[27] Database for B thalassemia in Arabs[28] Israeli National genetic bank contains genetic mutations of Arabs[29] Teebi database 2002[30] 2010 genes responsible for genetic diseases among Palestinian Arabs[31][32] The next Pan-Arab conference Nov 2013 [33]

## Diagnosis of genetic disorders[edit]

Diagnosis of genetic disorders after birth is done by clinicians, lab tests, and sometimes genetic testing. Genetic testing profiling screening of pregnant women's fetuses for List of disorders included in newborn screening programs using Microchip Genetic Microarrary might help detect genetic mutations incompatible with life and determining abortion. Some genetic tests of born children might help finding the right treatment.[34][35] Mothers could test for genetic disorders in the fetus by method of chorionic villus sampling (CVS) or amniocentesis.

## Genealogy and geography[edit]

Consanguinity (interbreeding, marriage between cousins, inside the family , the clan, the tribe, or even country especially small countries like Kuwait, to preserve fortunes in the family or clan or tribe especially after the Oil discovery in Gulf) is the main cause of Arabic genetical diseases, in addition to mutagens such as environmental factors such as the oil industry and radiological waste dumps in sea and land. Most affected are the small countries such as Kuwait Jordan and the Gulf states, but all other Arabic countries because of Consanguinity. Consanguinity also is causing Novel new diseases that are unpredictable and extremely costly to diagnose and treat ( where treatments of genetic diseases are still lacking), and the level of genetic mutations (causing mostly novel diseases) carriers is astounding! ( for example 70% of Saudis carry mutations that cause Mental disability disorders). Intellectual disability, neurogenetic disorders, blood and bleeding disorders and rare genetic diseases and retinal dystrophy and novel candidate disease marker variations.while Saudi mtDNA association with obesity. Intellectual disability comes first with the combined and observed carrier frequency of 0.06779!, followed by retinal dystrophy, glaucoma, inborn errors of metabolism, sickle cell disease/thalassemia, deafness, dysmorphic/dysplasia, ataxia, myopathy/muscular dystrophy, polycystic kidney disease/nephronophthisis, Joubert syndrome/Meckel-Gruber syndrome, carbonic anhydrase II deficiency, cystic fibrosis, Bardet-Biedl syndrome, and cataract. Carrier frequency of the intellectual disability is three times more than that of sickle cell disease and thalassemia among the Arab population with 25–60% consanguinity rates!. 33 genes (observed phenotype), were identified among the pre-screened multiplex consanguineous families with neurogenetic disorders. Previously known Blood and bleeding disorders: Molecular defects, blood disorders, β-thalassemia, sickle cell disorder, α-thalassemia and G6PD (glucose-6-phosphate dehydrogenase) deficiency are the most common in the Arab population. Familial transthyretin amyloidosis Fetal death and perinatal death caused by genetic heterogeneity. Microphthalmia. "diagram showing Arabic genetic diseases in order in Qatar".

Since Arabic populations tend to have Arabic paternal ancestry, mainly the Arabian male Y- J1 haplogroup especially j1-P58 and little E1b1b of North Africa, more diverse maternal ancestries needed to balance and to diverse the gene pool, but "historically" poor countries such as Yemen and Arabian peninsula lack female ancestry diversity, as seen most in greater Syria Iraq and Egypt that have extra maternal haplogroups than the Middle East- associated maternal (aka mito or mitochondrial) HV1b, U, U5, M1, R0a haplogroups, and the traditional Consanguinity that had increased due to oil fortune preservation trend, significantly trumped up the genetic diseases and genetic predisposition for such diseases that are becoming Novel "new" in nature, ie unknown yet to discover and understand the etiology and prepare treatments or prevention. The new trend to stay local among Arabic populations in Arabic countries and especially after creating small countries after independence from the west in the 50s.Marrying into a different gene pool such as historically isolated Yemen or different and isolated ie Indonesia would help. while Diabetes is very prevalent among Arabs 10% up to 20% , responsible Arab genes have not been found yet but Saudi mitochondrial gene was found that cause obesity that predispose to Diabetes.[36][37]

Bare lymphocyte syndrome high in western Arabic block Morocco, type II limb-girdle muscular dystrophy, type 2C in Libya, hemolytic-uremic syndrome in Saudia, ankylosing spondylitis in Egypt and East block, alpha-thalassemia in all countries except Egypt, Syria, and Iraq, cystic fibrosis in Iraq Saudi Yemen Libya Morocco, familial Mediterranean fever fmf in east block and Libya Morocco, beta thalassemia in all countries, g6dh deficiency all countries.[18]

Most genetic markers of Arabs' genetic diseases are phenotypic, i.e. specific mutations of Arab peoples, especially in countries. Even though genetic mutations of Gulf states are mostly the same, but some genetic phenotypes are Kuwaiti etc.

The diseases have geographical distribution among Arab countries such as greater Syria, Gulf states, Yemen, Western block (Morocco, Algeria, Tunisia), because of the restricted marriages to each block or even to one country. Moreover, cousin marriages (consanguinity) and endogamy (marriages restricted to minority sects) exacerbate the problem. Distancing of marriages from distant gene pools might help resolve the problem in Arabic countries. Many of the pronounced genetic deficiencies in Arabs are located on HLA segment on chromosome 6. This same segment mutations are markers of Arabs in Genealogical and forensic profiling tests and studies. Such studies as:[14][38][39][40][41] Arab population data on the PCR-based loci:HLA [42] HLA polymorphism in Saudi.[43]

Since over 70% of Arab genetic disorders are autosomal-recessive, meaning the defective gene has to be found in both father and mother, and since the gene pool is similar in population (males and females alike since autosomal chromosomes are admixture from father and mother, in closed societies (marriages from same sect endogamy, or same tribe or even from same country, or even from the same block of countries since it is similar in geographical blocks as shown in the online brochures referenced above.[44]

## Founder Effect Arabic mutations causing Diseases[edit]

The following are diseases that can happen to genetic mutations that have ancient ancestry founding effect mutations that happened in Arabic Ancestry ( not including the many Novel new mutations caused by Consanguinity and unknown factors in recent times):[45]

Sickle cell Anemia Hydroxylaze deficiency Ataxia with vitamin E deficiency Genetic hetero intestinal malabsorption B12 Autosomal recessive Hearing loss Autosomal recessive deafness Alpha and Betha Thalassemia Carbonic anhidrase deficiency, Familial Mediterranean fever, Fragile X syndrome, Gaucher disease, Glucose 6 phosphatase dihedrogenase deficiency, Hereditary Hemochromatosis, Limbs Girdle Muscular deficiency type c, Megalo plastic anemia, Parkinson's, Phenylketonuria Primary hyperocaluria Congenital Myasthenia Syndrome Criger- Najjar Type I syndrome Distal Renal tubero Acidosis Sickle Haemoglobin G6pd deficiency A and B Thalassemia Defnb1 Phenylketonuria PAH Distal Renal tubular Acidosis Cystic fibrosis Leber congenital Autosomal recessive myopathy inclusion body Mitochondrial gene for obesity in Saudis that along with sedentary life predispose to Diabetes.

## Prevention[edit]

To use Genetic counseling especially before and after marriage, avoiding Consanguinity, marrying into a different gene pool especially that did not have Consanguinity. Avoiding mutagens ie factors that cause mutations such as radioactive and other environmental factors. The importance to report to the medical provider the ethnicity As Arabic or Berber and specific country such as Saudi Arabia so the provider can design genetic testing and other tests to discover the possible ailments especially large DNA sequencing and specific DNA testing became available and reasonably affordable. Most genetic diseases go unnoticed by person or physician or dormant and show up later in life, and so genetic testing might reveal the probable existence or dormancy of a disease or syndrome before it manifest or to confirm a disease in spite of negative other non genetic laboratory tests. many disease causing genetic alterations are country specific or even sub category such as " Jewish Tunisian" for example. knowing the ancestral Y paternal and mitochondrial maternal haplogroups and other private companies Nuclear DNA might give Bird's eye view of what to expect along with self identification of race and country of origin.

## Discoveries of new syndromes[edit]

Teebi type of hypertelorism (1987) •• Teebi Shaltout syndrome (1989) •• Al Gazali syndrome (1994) •• Megarbane syndrome (2001)

There are even new Arabic names for emerging genetic disorders and syndromes like:

Spectrum of Genetic Disorders in Arabs •• Lebanese type of mannose 6--phosphate receptor recognition defect (1984) •• Algerian type of spondylometaphyseal dysplasia (1988) •• Kuwaiti type of cardioskeletalsyndrome (1990) •• Yemenite deaf-blind hypopigmentation syndrome (1990) •• Nablus mask-like facial syndrome (2000) •• Jerash type of the distal hereditary motor neuropathy (2000) •• Karak syndrome (2003) •• Omani type of spondyloepiphy.[46]

## Uniparental markers[edit]

Main articles: Y-DNA haplogroups in populations of the Near East and Y-DNA haplogroups in populations of North Africa

### Y-chromosome[edit]

The most dominant Paternal Y haplogroup in Arabic countries is the Arabian J1 haplogroup AKA J-M267 and especially its main clade J1-P58 reaching up to 80% in some countries like Yemen Qatar and Sudan, according to latest samples studies. [47] J1-M267 that is not P58 are found in Yemen and Oman. The mutation STR DYS388 equal or above 16 found in J1-p58 was used as genetic profiling in Forensics since the 80s to determine Middle Eastern ancestry. (Nebel et Al 2001)[48]

Below is the general distribution of Y-DNA haplogroups among populations native to the Arab world:

Population | Language Family[49] | n[50] | R1b[51] | n | R1a | n | I | n | E1b1b | n | E1b1a | n | J | n | G | n | N | n | T | n | L

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Arabs (Algeria)  | Afro-Asiatic (Semitic)  | 35  | 13.0[52] | 35  | 0.0[52] |  |  | 32  | 50[53] |  |  | 35  | 35[52] |  |  |  |  |  |  |  |
Arabs (Algeria – Oran)  | Afro-Asiatic (Semitic)  | 102  | 10.8[54] | 102  | 1[54] |  |  | 102  | 50.9[54] | 102  | 12.8[54] | 102  | 27.4[54] |  |  |  |  |  |  |  |
Arabs (Bedouin)  | Afro-Asiatic (Semitic)  | 32  | 0.0[55] | 32  | 9.4[55] | 32  | 6.3[55] | 32  | 18.7[55] |  |  | 32  | 65.6[55] |  |  |  |  |  |  | 32  | 0.0[55]
Arabs (Iraq)  | Afro-Asiatic (Semitic)  |  | 10.8[56] |  | 6.5[56] |  |  | 218  | 8.3[53] | 218  | 0.9[53] | 156  | 50.6[53] |  |  |  |  |  |  |  |
Arabs (Israel)  | Afro-Asiatic (Semitic)  | 143  | 8.4[55] | 143  | 1.4[55] | 143  | 6.3[55] | 143  | 20.3[55] |  |  | 143  | 55.2[55] |  |  |  |  |  |  | 143  | 0.0[55]
Arabs (Morocco)  | Afro-Asiatic (Semitic)  | 44  | 3.8[57] | 44  | 0.0[57] | 44  | 0.0[57] | 49  | 85.5[53] |  |  | 49  | 20.4[53] |  |  |  |  |  |  |  |
Arabs (Oman)  | Afro-Asiatic (Semitic)  | 121  | 1.7[58] | 121  | 9.1[58] | 121  | 0.0[58] | 121  | 15.7[58] | 121  | 7.4[58] | 121  | 47.9[58] | 121  | 1.7[58] |  |  | 121  | 8.3[58] | 121  | 0.8[58]
Arabs (Qatar)  | Afro-Asiatic (Semitic)  | 72  | 1.4[59] | 72  | 6.9[59] | 72  | 0.0[59] | 72  | 5.6[59] | 72  | 2.8[59] | 72  | 66.7[59] | 72  | 2.8[59] | 72  | 0.0[59] | 72  | 0.0[59] | 72  | 2.8[59]
Arabs (Saudi Arabia)  | Afro-Asiatic (Semitic)  | 157  | 1.9[60] | 157  | 5.1[60] | 157  | 0.0[60] | 157  | 7.6[60] | 157  | 7.6[60] | 157  | 58.0[60] | 157  | 3.2[60] | 157  | 0.0[60] | 157  | 5.1[60] | 157  | 1.9[60]
Arabs (UAE)  | Afro-Asiatic (Semitic)  | 164  | 4.3[59] | 164  | 7.3[59] |  |  | 164  | 11.6[59] | 164  | 5.5[59] | 164  | 45.1[59] | 164  | 4.3[59] | 164  | 0.0[59] | 164  | 4.9[59] | 164  | 3.0[59]
Arabs (Yemen)  | Afro-Asiatic (Semitic)  | 62  | 0.0[59] | 62  | 0.0[59] | 62  | 0.0[59] | 62  | 12.9[59] | 62  | 3.2[59] | 62  | 82.3[59] | 62  | 1.6[59] | 62  | 0.0[59] | 62  | 0.0[59] | 62  | 0.0[59]
Arabs (Syria)  | Afro-Asiatic (Semitic)  | 20  | 15.0[61] | 20  | 10.0[61] | 20  | 5.0[61] | 20  | 10.0[61] |  |  | 20  | 53.0[61] | 20  | 0.0[61] | 20  | 0.0[61] | 20  | 0.0[61] | 20  | 0.0[61]
Arabs (Lebanon)  | Afro-Asiatic (Semitic)  | 31  | 6.4[61] | 31  | 9.7[61] | 31  | 3.2[61] | 31  | 25.8[61] |  |  | 31  | 45.2[61] | 31  | 3.2[61] | 31  | 0.0[61] | 31  | 0.0[61] | 31  | 3.2[61]
Arabs (Sudan)  | Afro-Asiatic (Semitic)  | 102  | 15.7[62] |  |  | 102  | 3.9[62] | 102  | 16.7[62] |  |  | 102  | 47.1[62] |  |  |  |  |  |  |  |
Arabs (Tunisia)  | Afro-Asiatic (Semitic)  | 148  | 6.8[52] | 148  | 0.0[52] | 148  | 0.0[52] | 148  | 49.3[52] | 148  | 1.4[52] | 148  | 35.8[52] |  |  | 148  | 0.0[52] | 148  | 0.7[52] | 148  | 0.0[52]
Arabs (Libya)  | Afro-Asiatic (Semitic)  | 63  | 3[63] | 63  | 1.5[63] | 63  | 1.5[63] | 63  | 52.0[63] | 63  | 0.0[63] | 63  | 24.0[63] | 63  | 8.0[63] |  |  | 63  | 5.0[63] | 63  | 1.5[63]
Saharawi (SADR)  | Afro-Asiatic (Semitic)  |  |  |  |  |  |  | 29  | 79.3[53] | 29  | 3.4[53] | 29  | 17.2[53] |  |  |  |  |  |  |  |
|  |  |  |  |  |  |  |  |  |  |  |  |  |  |
Egyptians | Afro-Asiatic (Semitic)  | 92-147  | 5.4[64]-4.1 | 92-147  | 0.0[64]-2.7[58] | 92-147  | 1.1[64]-0.7[58] | 92-147  | 43.5[64]-36.7[58] | 92-147  | 3.3[64]-2.8[58] | 92-147  | 22.8[64]-32.0[58] | 92-147  | 2.2[64]-8.8[58] | 92-147  | 0.0[64]-0.0[58] | 92-147  | 7.6[64]-8.2[58] | 92  | 0.0[64]
Egyptians (North)  | Afro-Asiatic (Semitic)  | 43  | 9.3[65] | 43  | 2.3[65] | 43  | 0.0[65] | 43  | 53.5[65] |  |  | 44  | 18.2[52] | 43  | 7.0[65] |  |  | 43  | 2.3[65] | 43  | 0.0[65]
Egyptians (South)  | Afro-Asiatic (Semitic)  | 47  | 13.8[66] |  |  |  |  | 47  | 78.7[66] |  |  |  |  |  |  |  |  |  |  |  |
Lebanese | Afro-Asiatic (Semitic)  | 914  | 8.1[67] | 914  | 2.5[65] | 914  | 4.8[65] | 914  | 16.2[65] | 914  | 0.7[65] | 914  | 46.1[65] | 914  | 6.6[65] | 914  | 0.1[65] | 914  | 4.7[65] | 914  | 5.2[65]

### mtDNA analysis[edit]

The maternal ancestral lineages of Arabic countries are very diverse. The original and still most prevalent maternal haplogroups of the Near East (Syria, Lebanon, Palestine, Iraq, Arabian Peninsula) and Egypt are mt (maternal) M1 haplogroup a branch of Asian Haplogroup M (mtDNA) which branched from L3 Haplogroup around 70 000 years ago. and (maternal) HV1 haplogroup a branch of HV1 haplogroup that are still high in Yemen, while in Greater Syria there is a Eurasian maternal gene flow, and U5 haplogroup [14][68][62]

### HLA antigens[edit]

Many of the genetic disorders specific to Arabs are located on HLA segment on chromosome 6. These same segment mutations are also markers of Arabs in genealogical and forensic profiling tests and studies.[69][70][14][68][62][71][72]

## Autosomal DNA[edit]

There are four principal West-Eurasian autosomal DNA components that characterize the populations in the Arab world: the Arabian, Levantine, Coptic and Maghrebi components.[citation needed] The Arabian component is the main autosomal element in the Gulf region. It is most closely associated with local Arabic-speaking populations.[73]

* The Arabian component is also found at significant frequencies in parts of the Levant and Northeast Africa.[73][74] The geographical distribution pattern of this component correlates with the pattern of the Islamic expansion, but its presence in Lebanese Christians, Sephardi and Ashkenazi Jews, Cypriots and Armenians might suggest that its spread to the Levant could also represent an earlier event.[73] A separate study by Iosif Lazarides and colleagues published in the same year, correlated this component with Epipaleolithic Natufians from the Levant. This study produced genome-wide ancient DNA from 44 ancient Near Easterners between ~12,000 and 1,400 BCE, including Natufian hunter–gatherers, and suggested an earlier spread of Natufian ancestry to populations of the Levant and the Eastern Mediterranean. Natufians were found to be of exclusive West-Eurasian origin, most closely related to modern Arabs, followed by Berber peoples.[75] A 2018 re-analysis of Natufian samples, including 279 modern populations as a reference, found that the Natufians were largely of local West-Eurasian origin, but harbored 6.8% Eastern African-related ancestry, specifically an Omotic component, which peaks among the Aari people. It is suggested that this Omotic component may have been introduced into the Levant along with the specific Y-haplogroup sublineage E-M215, also known as "E1b1b", to Western Eurasia.[76]

* The Levantine component is the main autosomal element in the Near East and Caucasus. It peaks among Druze populations in the Levant. The Levantine component diverged from the Arabian component about 15,500-23,700 ypb.[73]

* The Coptic component peaks among Egyptian Copts in Sudan.[citation needed]

* The Maghrebi component is the main autosomal element in the Maghreb. It peaks among the non-Arabized Berber populations in the region.[74] The modern Northern African (Berber) populations have been described as a mosaic of Northern African (Maghrebi), Middle Eastern, European, and Sub-Saharan African-related ancestries.[77]

A genetic study published in the "European Journal of Human Genetics" in Nature (2019) showed that Middle Easterners (Arabs) are closely related to Europeans and Northern Africans as well as to Southwest Asians.[78] The "Arab macropopulation" is generally closely related to other "West-Eurasian" populations, such as Europeans or Iranian peoples. The Arab expansion marked one of the last expansions of West-Eurasian ancestry into Africa, with the earliest scientifically attested West-Eurasian geneflow into Africa being dated back to 23,000 BCE (or already earlier), and may be associated with the spread of Proto-Afroasiatic from the Middle East.[79][80] Hodgson et al. 2014 found a distinct non-African ancestry component among Northeastern Africans (dubbed "Ethio-Somali"), which split from other West-Eurasian ancestries, most closely to the Arabian ancestry component, about 23,000 years ago, and migrated into Africa pre-agricultural (between 12,000 to 22,000 years ago). This component is suggested to have been present in considerable amounts among the Proto-Afroasiatic-speaking peoples. The authors argue that the Ethio-Somali component and the Maghrebi component descended from a single ancestral lineage, which split from the Arabian lineage and migrated into Africa from the Middle East. In Africa, this West-Eurasian lineage diverged into the Maghrebi component, predominant in Northern Africa, and the Ethio-Somali component, found in significant varying degrees among populations of the Horn of Africa.[81]

In 2021, a study showed no genetic traces of early expansions out-of-Africa in present-day populations in the Near-East, but found Arabians to have elevated Basal Eurasian ancestry that dilutes their Neanderthal ancestry.[82]

## See also[edit]

* Arab people
* Arab studies
* Arabization
* DNA history of Egypt
* Genetic history of the Middle East
* Genetic history of North Africa
* Genetic studies on Jews
* Genetic studies on Moroccans

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## Further reading[edit]

* Teebi AS (2010). Genetic Disorders Among Arab Populations (2nd ed.). Berlin, Heidelberg: Springer. ISBN 978-3-642-43475-4.

## External links[edit]

* "The Centre for Arab Genomic Studies (CAGS)".

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