Allelic Polymorphisms of Killer Immunoglobulin-Like Receptor Genes in Malay and Orang Asli Populations of Peninsular Malaysia

Next-generation DNA sequencing (NGS) technology advancements provide new insight into the level of variation in killer immunoglobulin-like receptor (KIR) genes. High resolution allele genotyping of seven KIR genes was conducted among 94 unrelated Malay and Orang Asli (OA) individuals of Peninsular Malaysia. A manual bioinformatics analysis is performed and optimised by Sanger sequencing method. The Malays expressed a total of 22 alleles, as compared to only 15 alleles in the OA population. In total, 12 centromeric and 9 telomeric allelic haplotypes were identified in the Malays, whereas 8 centromeric and 5 telomeric allelic haplotypes were identified in the OA. The KIR2DL1, KIR2DL3, and KIR2DS4 genes exhibited a high degree of variation and balanced distribution in the Malay and OA populations. On the other hand, KIR2DL4, KIR3DL1, KIR3DL2 and KIR3DL3 genes exhibited a high degree of conservation, with less number of alleles identified and the dominance of a single allele at high frequency. High-resolution KIR allele genotyping has revealed unique sequence variations and allelic haplotypes between individuals and populations. The distributions of KIR alleles and haplotypes are useful for genetic population studies and serve as a baseline for future transplantation matching and disease association research.     

Conflicts regarding genetic counseling for fragile X syndrome screening: a survey of clinical geneticists and genetic counselors in Israel

Although fragile X screening has been offered in Israel since 1994, issues related to potential neurological and gynecological symptoms in carriers make counseling for fragile X different from recessive disorders. We evaluated the attitudes of clinical geneticists and genetic counselors regarding genetic counseling given to the women undergoing screening. We performed a self‐administered questionnaire including 13 study questions mailed to all clinical geneticists and genetic counselors in Israel. The questions were related to counseling for women pre‐ and post‐screening regarding themselves and the affected fetuses (including the risk for premature ovarian insufficiency; FXPOI and fragile X‐associated tremor ataxia syndrome; FXTAS). Out of a total of 80 clinical geneticists and genetic counselors, 34 responded with no additional responses on e‐mail re‐call. There was no clear consensus for 11/13 (85%) presented questions. The most striking differences in opinion were observed for issues regarding FXTAS risk in pre‐screening counseling sessions (P < 0.05). This study demonstrates that, there is no consensus on critical variables implying risk for fetus and mother and that counseling practices are dissimilar even in this small cohort of experts. We demonstrated a conflict between the detailed amount of information, which should be given prior to the test in order to allow informed decisions and the overload of information, which may cause confusion. © 2011 Wiley‐Liss, Inc.     

Screening for disease in the newborn: the evidence base for blood-spot screening

This paper reviews the evidence of benefit resulting from newborn screening in Australia as well as for some of those disorders not yet included in the Australian panels, and discusses briefly disorders under active consideration for inclusion in the screening panels.There is solid evidence of benefit from newborn screening for phenylketonuria, congenital hypothyroidism, cystic fibrosis, and overall for the disorders included in tandem mass spectrometry screening. There is also some evidence of benefit for several disorders not screened for in Australia, including congenital adrenal hyperplasia. Harms resulting from screening include anxiety related to false positive results; adverse effects of unwarranted treatment for mild variants; unwanted genetic information; and the costs (opportunity costs) of screening. For well-run programs these harms are relatively small.Screening could become more effective with the development of good systems for rational consideration of disorders to be included, with the extended use of second tier testing to reduce the false positive rate, and with research on the most effective way to deal with mild variants. The most important aspect of increasing effectiveness is the full integration of the screening program, diagnostic laboratories, and the clinical service. This is already in place in Australasia.     

HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample

Human Leucocyte Antigen F (HLA-F) is a non-classical HLA class I gene distinguished from its classical counterparts by low allelic polymorphism and distinctive expression patterns. Its exact function remains unknown. It is believed that HLA-F has tolerogenic and immune modulatory properties. Currently, there is little information regarding the HLA-F allelic variation among human populations and the available studies have evaluated only a fraction of the HLA-F gene segment and/or have searched for known alleles only. Here we present a strategy to evaluate the complete HLA-F variability including its 5′ upstream, coding and 3′ downstream segments by using massively parallel sequencing procedures. HLA-F variability was surveyed on 196 individuals from the Brazilian Southeast. The results indicate that the HLA-F gene is indeed conserved at the protein level, where thirty coding haplotypes or coding alleles were detected, encoding only four different HLA-F full-length protein molecules. Moreover, a same protein molecule is encoded by 82.45% of all coding alleles detected in this Brazilian population sample. However, the HLA-F nucleotide and haplotype variability is much higher than our current knowledge both in Brazilians and considering the 1000 Genomes Project data. This protein conservation is probably a consequence of the key role of HLA-F in the immune system physiology.