Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific

Abstract

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI*A and CFI*B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI*A was divided into two suballeles, CFI*As (R201S) and CFI*Ah (R406H). CFI*Aj, a rare variant allele originating from CFI*Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI*As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI*Ah, prevailed almost exclusively in East Asians and was observed at the highest frequencies in southern Chinese Han and Thais. CFI*Ah must have arisen 123J Hum Genet (2008) 53:1016-1021 DOI 10.1007 in a southeastern part of Asia and thereafter have spread to neighboring populations.

Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency

“…Japanese patient (ID 13) with renal insufficiency carried the one Japanese-specific CFI missense mutation, p.R201S, which is a low frequency mutation with a MAF of 2% in the Japanese population [19]. The remaining 7 missense mutations were classified as common mutations with a MAF of more than 5%.…”

“…On the basis of the CFI crystal structure, the low frequency mutation CFI:p.R201S resides on the surface region of the protein away from the proposed cofactor and/or substrate interaction sites, indicating a non-dysfunctional mutation [23]. This mutation is found only in Far East populations including Japanese [19].…”

HERC1 polymorphisms: population‐specific variations in haplotype composition

“…Most of these samples were from a set used in previous studies. 7,8 DNA samples from three chimpanzees were also investigated to determine the ancestral haplotype. This study was approved by the Ethical Committee at the Faculty of Medicine, Tottori University.…”

“…These SNPs were simultaneously genotyped by quadruplex PCR based on the APLP method. [7][8][9] The nucleotide sequence and final concentration of each primer are shown in Table 2. The PCR cocktail consisted of 50 ml of Multiple PCR Master Mix from a Multiplex PCR Kit (Qiagen, Hilden, Germany), 6.4 ml of 12 primers with a concentration of 100 pmol/ml, and 43.6 ml of water.…”

A hypervariable STR polymorphism in the complement factor I (CFI) gene: Asian-specific alleles

“…African, and East Asian-specific nonsynonymous singlenucleotide polymorphisms (SNPs) in exons 4 (c.A603C), 7 (c.G898A), and 11 (c.G1217A) [3]. An STR with 27 repeats of the tetranucleotide polypyrimidine TTTC unit exists in intron 7 of this gene.…”