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The expression of the Duffy Antigen/Receptor for Chemokines (DARC) on red blood cells (RBC) has been commonly determined using hemagglutination tests. Because the vast majority of African individuals are Duffy-negative, screening for DARC expression on RBC is a valuable tool to assess Caucasian admixture in populations of African descent. Furthermore, blood group antigens have been frequently tested as potential risk factors for complex diseases. We established a dot-blotting protocol using sequence-specific oligonucleotides (SSOs) for the DARC-46T (“Duffy-positive”) and -46C (“Duffy-negative”) alleles. With this method, but not with serological methods, Duffy-positive individuals can be further characterized as homozygous or heterozygous for the dominant Duffy-positive allele, allowing more precise estimation of allele frequencies and admixture in heterogeneous populations. In unrelated African American ( n = 235), Afro-Caribbean ( n = 90) and Colombian ( n = 93) subjects, the frequency of the -46T allele was 21.7%, 12.2% and 74.7%, respectively. The percentage of Duffy-positive individuals (homozygous or heterozygous for the −46T allele) in each population was in accordance with published frequencies. As expected, the -46C allele was not detected in 20 Caucasian subjects. This sensitive and specific method allows for the rapid and inexpensive screening of large samples for Duffy genotypes using small quantities of genomic DNA.

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.

SM22 is a 22-kDa protein identified variously as SM22, transgelin, WS3-10, or mouse p27. Though its precise function is unknown, it is abundant in smooth muscle and so may contribute to the physiology of this widespread tissue. We found that cosmid 16b6 contains the entire 5.4-kb, five-exon human SM22 gene (HGMW-approved symbol, TAGLN), and we cytogenetically localized the gene to chromosome 11q23.2. Northern analysis of human adult tissues showed that SM22 mRNA is most prevalent in smooth muscle-containing tissues, but is also found at lower levels in heart. The human SM22 promoter contains nuclear factor-binding motifs known to regulate transcription in smooth muscle, and human SM22 promoter-luciferase reporter constructs exhibited high transcriptional activity in A7r5 or primary canine aortic smooth muscle cells, but show little activity in nonmuscle COS7 cells. In addition, human SM22 promoter activity increased by two- to threefold upon serum stimulation of nonmuscle cells.

HLA-G is a nonclassical, class I HLA gene that is primarily expressed by fetal cells at the maternal-fetal interface and is thought to play a key role in the induction of tolerance in pregnancy. This paper reports the identification of a single base pair deletion at position 1597 (1597de1C) in exon 3 (encoding the α2-domain) of HLA-G on 20 of 272 (7.4 per cent) African American chromosomes, three of 102 (2.9 per cent) Hispanic chromosomes, and none of 134 Caucasian chromosomes. This relatively common frameshift mutation results in amino acid substitutions in all of the residues in the second half of exon 3 including the conserved cysteine at codon 164. An adult individual was identified who was homozygous for this ‘null’ allele, and a first trimester placenta that was homozygous for 1597de1C had no detectable HLA-G1 protein. These data indicate that expression of HLA-G1 protein is not essential for fetal survival.