&lt;i&gt;LRRK2&lt;/i&gt; G2019S in the North African Population: A Review

Benamer, Hani Ts; Silva, Rajith de

doi:10.1159/000279653

Cited by 54 publications

(43 citation statements)

References 33 publications

(33 reference statements)

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“…In the North African Arab population upwards of 30% of PD patients have been shown to harbour the LRRK2 G2019S mutation, and all these individuals share a common haplotype. [19] This same mutation is also present at a relatively high frequency (~20%) in Ashkenazi Jews, implicating a founder effect for the mutation which occurred in the Near East at least 4 000 years ago. [20] In Norway, G2019S mutation carriers could be traced back 10 generations to a common Norwegian ancestor couple living between 1580 and 1650.…”

Section: Discussionmentioning

confidence: 96%

Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

et al. 2014

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Afrikaners in South Africa (SA) are a recognisable group with a relatively small gene pool and excellent family records over a period of >350 years. The foundations of this group were laid mainly from 1652 until 1807. Afrikaners are derived from settlers from The Netherlands (roughly one-third), Germany (slightly less than onethird) and France (roughly one-quarter), with smaller contributions from other countries, imported slaves and indigenous peoples, [1] the exact proportions differing for each present-day Afrikaner. To illustrate this, a 'deconstruction' of one specific Afrikaner individual who has an incomplete ancestral chart of 926 individuals shows contributions of 37.5% from The Netherlands, 27.4% from Germany and 26.4% from France in his make-up, with 2.2% from people 'van die Kaap' ('from the Cape' , an expression which usually refers to female slaves born in the Cape), 1.9% from Britain and the rest from other countries.[2] There could be a perception that in isolated areas such as the Gamkaskloof more frequent intermarriages might have had an influence on the occurrence of hereditary diseases. However, there is no clear evidence that the people in these areas differed significantly from those in less isolated rural Afrikaner communities. [3] Several disorders among Afrikaners occur at relatively high frequencies due to founder effects. [3,4] A founder effect results when a small subset of a large population establishes a new population. The new population may differ significantly from the original population, both in terms of its genotypes and phenotypes. In the case of Afrikaners, the disorders that occur at an unusually high frequency may indicate that the original Dutch, French and German colonists who settled in the Cape carried those disease-causing genes at high frequency. In some cases the diseases can be traced back to specific founder couples, e.g. for familial colonic polyposis, [4,5] porphyria variegata, [6] progressive familial heart block, [7] Huntington's disease (HD), [8] osteogenesis imperfecta, [9] pseudoxanthoma elasticum (PXE), [10] schizophrenia, [11] long QT syndrome [12,13] and Fanconi's anaemia. [14] Given the evidence of founder effects for other disorders in the Afrikaner population, we sought to determine whether a founder effect for Parkinson's disease (PD) also occurs in this population. PD is a debilitating neurodegenerative condition arising as a result of the progressive loss of dopaminergic neurons in the brainstem associated with proteinaceous inclusions termed Lewy bodies. Cardinal clinical features include resting tremor, rigidity, bradykinesia, postural instability and responsiveness to levodopa. A genetic aetiology has been found in ~10 -15% of PD cases and a number of genes (and corresponding proteins) have been implicated, including parkin, PINK1 (PTEN-induced putative kinase 1), DJ-1 (DJ-1), SNCA (α-synuclein), LRRK2 (leucine-rich repeat kinase 2), VPS35 (vacuolar protein sorting 35) and EIF4G1 (eukaryotic translation initiation factor 4 γ1).For the genetic fo...

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Section: Discussionmentioning

confidence: 96%

Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

et al. 2014

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“…Very rare in East Asia, it accounts for about 15% in Ashkenazi Jews (Ozélius et al, 2006) and for 4% in North African Arabs (Lesage et al, 2006;Change et al, 2008;Benamer and De Silva, 2010). The marked ethic differences in risk conferred by the G2019S mutation might result from the frequency of G2019S, or (/and) from (1,650-3,120) 3,120 (2,340-4,620) 3,840 (3,210-5,400) …”

Section: Discussionmentioning

confidence: 99%

New contribution on the <i>LRRK2</i> G2019S mutation associated to Parkinson’s disease: age estimation of a common founder event of old age in Moroccan Berbers

Lucotte¹,

Dávid²,

Change³

2012

Int.J.Mod.Anthrop

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-Background:The LRRK2 G2019S mutation is an important genetic determinant of Parkinson's disease (PD) across the world that occurs at an elevated frequency in North Africa. Aim: To estimate the date of the G2019S mutation in Berbers. Material and Methods: We determined the LRRK2 haplotypes in twenty-two G2019S carriers, mostly North Africans, and in one hundred twenty-four Arab, Moroccan Berber and Sephardi Jew controls, using seven microsatellite and two SNP genetic markers. Results: A single haplotype was detected, with some variations, in all mutation carriers. Using a maximum-likelihood method, we estimate that Moroccan Berbers with G2019S share a common ancestor who lived ~128 (95% CI 107-180) generations ago. Conclusion: Our conclusion is that the G2019S mutation of the LRRK2 gene originates 3,840 (95% CI 3,210-5,400) years ago in parkinsonian Moroccan Berbers patients.

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“…Several of these mutants, such as R1441C, G2019S and I2020T have been described to show increased kinase activity (West et al, 2005;Gloeckner et al, 2006). The G2019S mutation in the kinase domain is the most common LRRK2 mutation and its frequency varies among different ethnic populations (Benamer and De Silva, 2010).…”

Section: Yeast Models To Study Parkinson's Disease Associated Genesmentioning

confidence: 99%

Yeast buddies helping to unravel the complexity of neurodegenerative disorders

Fruhmann

Seynnaeve

Zheng

et al. 2017

Mechanisms of Ageing and Development

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<i>LRRK2</i> G2019S in the North African Population: A Review

Cited by 54 publications

References 33 publications

Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

Identification of a common founder couple for 40 South African Afrikaner families with Parkinson’s disease

New contribution on the <i>LRRK2</i> G2019S mutation associated to Parkinson’s disease: age estimation of a common founder event of old age in Moroccan Berbers

Yeast buddies helping to unravel the complexity of neurodegenerative disorders

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