An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover.
We have now determined the molecular genetic basis for the common biochemical polymorphism at the adenosine deaminase (ADA) locus. The ADA*2 allele contains a G to A transition at nt22 (relative to the ATG) that results in substitution of asparagine for aspartic acid at codon 8 (Asp8Asn). Introduction of the nucleotide substitution into an ADA 1 cDNA and transfection into monkey kidney (Cos) cells confirmed that the mutation resulted in expression of an enzyme that comigrated with the naturally occurring ADA 2 allozyme. The substitution of neutral asparagine for anionic aspartic acid is consistent with the more cathodal electrophoretic migration of ADA 2 as compared with ADA 1. The nucleotide substitution was found on at least two different genetic backgrounds, suggesting independent recurrence of the mutation. Consistent with independent recurrence, the G to A transition is at a CpG dinucleotide and represents a type of mutation that occurs with high frequency. We have also unexpectedly identified a probable intragenic crossover in the very large first intron that is rich in repetitive DNA sequences.
New York University Medical Center, Department of Medicine, NY 10016.
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Hirschhorn
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Yang
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Israni
D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics*; D000483:Alleles; D001216:Asparagine; D001483:Base Sequence; D002460:Cell Line; D003434:Crossing Over, Genetic; D005091:Exons; D005260:Female; D005796:Genes / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics
D001216:Asparagine; D000243:Adenosine Deaminase