As part of our comprehensive genetic study of the aboriginal Taiwanese (Gaoshan), we have reported the distribution of allele frequencies for 13 red cell enzyme and 4 serum protein polymorphisms in all nine aboriginal groups. In this study, 10 additional serum protein polymorphisms for AHSG, C3, C6, C7, GC, HP, ITIH1, PI, TF and ZAG were typed. Common and variant alleles prevailing in East Asian populations were found together with several new variants. The distribution of allele frequencies differed markedly among the nine aboriginal groups and from that in East Asian populations. The large diversity among the aboriginal groups was confirmed by analysis of the genetic affinity on the basis of Nei's standard genetic distance and Cavalli-Sforza's chord distance, which were calculated using the present and previous data from 27 red cell enzyme and serum protein loci. The analysis based on 15 red cell enzyme and serum protein loci revealed that they, in particular the Puyuma and Ami, had strong affinity with Filipino among several East Asian populations.
DNA fragmentation factor beta (DFFB) polypeptide, endonuclease G (EndoG), and Flap endonuclease-1 (FEN-1) are responsible for DNA fragmentation, a hallmark of apoptosis. Although the human homologs of these genes show three, four, and six nonsynonymous single-nucleotide polymorphisms (SNPs), respectively, data on their genotype distributions in populations worldwide are limited. In this context, the objectives of this study were to elucidate the genetic heterogeneity of all these SNPs in wide-ranging populations, and thereby to clarify the genetic background of these apoptosis-related endonucleases in human populations. We investigated the genotype distribution of their SNPs in 13 different populations of healthy Asians, Africans, and Caucasians using novel genotyping methods. Among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene. All 6 SNPs in the FEN-1 gene were entirely monoallelic. Although it remains unclear whether each SNP would exert any effect on endonuclease functions, these genes appear to exhibit low degree of genetic heterogeneity with regard to nonsynonymous SNPs. These findings allow us to conclude that human apoptosis-related endonucleases, similarly to other human DNase genes, revealed previously, are well conserved at the protein level during the course of human evolution.
Abstract Deoxyribonucleases (DNases) have been suggested to be implicated in the pathophysiology of autoimmune diseases. In the DNASE1L3 gene encoding human DNase I‐like 3 (DNase 1L3), a member of the DNase I family, only two non‐synonymous (R178 H and R206C) single nucleotide polymorphisms (SNPs) have been examined [Ueki et al., Clin. Chim. Acta 2009, 407 , 20–24]. Three other non‐synonymous (G82R, K96N, and I243M) and four synonymous (S17S, T84T, R92R, and A181A) SNPs, in addition to R206C and R178H, have been identified in DNASE1L3 . We investigated the distribution of all these SNPs in exons of the gene in eight Asian, three African, and three Caucasian populations worldwide using newly devised genotyping methods. SNP T84T showed polymorphism in all the populations, and R92R was polymorphic in the three African and three Caucasian populations; R206C was distributed only in Caucasian populations. In contrast, no minor allele was found in five SNPs (S17S, G82R, K96N, A181A, and I243M) in DNASE1L3. Generally, the DNase 1L3 gene shows relatively low genetic diversity with regard to exonic SNPs. When the effect of amino acid/nucleotide substitutions resulting from the SNPs on DNase 1L3 activity was examined, none of the synonymous SNPs had any effect on the DNase 1L3 activity, whereas among non‐synonymous SNPs, SNP G82R diminished the activity of the enzyme, being similar to R206C. These findings permit us to assume that, although only R206 exhibits polymorphisms in a Caucasian‐specific manner, at least SNPs G82R and R206C in DNASE1L3 might be potential risk factors for autoimmune disease.
Incontinentia pigmenti in female identical twins is reported. The first baby showed the typical pigmentation of incontinentia pigmenti, while the second baby had hydrocephalus (colpocephaly) without pigmentation. They were identical, with a rate of 99.9% in 18 blood-type studies. Virus was not detected and cytogenetic studies proved normal. Both showed peripheral eosinophilia. The individual expressions of Incontinentia pigmenti in these identical twins were separated into cutaneous lesions and lesion of the central nervous system (intra-uterine hydrocephalus). Cutaneous lesions developed after birth. Twins with Incontinentia pigmenti are extremely rare and in this family showed different expressions of this disease in space and time.
Human orosomucoid (ORM) is composed of two tightly linked loci, ORM1 and ORM2, located on chromosome 9q. Some haplotypes contain duplicated ORM1 or ORM2. The present study using isoelectric focusing has revealed seven ORM haplotypes including new variants and/or silent alleles detected in eight Japanese families. ORM1*5.2-ORM2*15 in combination with common ORM1*1-ORM2*1 produced a five-band pattern. ORM1*5-ORM2*1 was observed in three families. ORM2*9 was coexistent with ORM1*1 or ORM1*2.1. ORM1*Q0 was linked to ORM2*1 or ORM2*14. ORM2*Q0 was suggested to be in association with ORM1*2. The ORM haplotypes with a silent gene must have arisen from unequal crossing-over between the tandemly duplicated genes of ORM.
