Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example.
The increased frequency of rare autosomal recessive conditions in genetically isolated populations is a well-established phenomenon. This genetic isolation is invoked as an explanation when one particular mutation is the sole or most frequent mutation observed in a given population and is referred to as the founder effect. This trend of allelic homogeneity is contrasted by an opposite trend when the consanguinity factor is in play. Independent of endogamy at the population level, a consanguineous union is sufficient to render homozygous a percentage of the genome that is directly correlated with the degree of consanguinity. Assuming the gene in question has a normal mutation rate, the resulting homozygosity will inevitably include different defective alleles of that gene. By reporting four novel alleles, we use Alström disease to exemplify the interesting observation of allelic heterogeneity for a very rare autosomal recessive disorder in a highly inbred population. While we frequently assume founder effect in inbred populations, this report should serve to remind us of the powerful effect of the consanguinity factor, a common confounding variable among some of those populations.
Aldahmesh
Mohamed A
MA
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Abu-Safieh
Leen
L
Khan
Arif O
AO
Al-Hassnan
Zuhair N
ZN
Shaheen
Ranad
R
Rajab
Mohammed
M
Monies
Dorota
D
Meyer
Brian F
BF
Alkuraya
Fowzan S
FS
D000483:Alleles; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D017093:Liver Failure / Q000235:genetics; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012529:Saudi Arabia; D013577:Syndrome
C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D011506:Proteins; D004247:DNA