Genetic characterisation of 13 rapidly mutating Y-STR loci in 100 father and son pairs from South and East Turkey.

BACKGROUND: Rapidly mutating (RM) Y-STRs recently emerged as a useful genotyping tool that can counteract problems normally associated with traditional Y-STRs. For instance, RM Y-STRs have the potential to differentiate Y-chromosomes from both close and distant paternal relatives. AIM: Characterisation of 13 RM Y-STR loci in a new sample pool from Turkey in terms of population genetic data and mutation rates. SUBJECTS AND METHODS: One hundred father-son pairs from South and East Turkey were genotyped. Based on the 99 father haplotypes unique to the current study, statistical parameters of forensic interest were computed. Nei's DA distances among 112 global population datasets were estimated and visualised by phylogenetic and multidimensional scaling (MDS) analyses. RESULTS: Fifteen father-son pairs were found to differ at a single locus and four at two loci, resulting in a differentiation rate of 19%. Mutations were observed at 10 out of 13 loci, with rates ranging from 1 × 10-2 to 6 × 10-2. CONCLUSION: Mutation rates and differentiation rates between the father-son pairs were similar to those from the literature. In contrast to previous work, novel phylogenetic tree construction results based on Nei's DA distances suggested a close correlation between the geographic and genetic distances observed, except for known cases of past mass migration events.

Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling.

Altered Bone Morphogenetic Protein (BMP) signaling leads to multiple developmental defects, including brachydactyly and deafness. Here we identify chondroitin synthase 1 (CHSY1) as a potential mediator of BMP effects. We show that loss of human CHSY1 function causes autosomal-recessive Temtamy preaxial brachydactyly syndrome (TPBS), mainly characterized by limb malformations, short stature, and hearing loss. After mapping the TPBS locus to chromosome 15q26-qterm, we identified causative mutations in five consanguineous TPBS families. In zebrafish, antisense-mediated chsy1 knockdown causes defects in multiple developmental processes, some of which are likely to also be causative in the etiology of TPBS. In the inner ears of zebrafish larvae, chsy1 is expressed similarly to the BMP inhibitor dan and in a complementary fashion to bmp2b. Furthermore, unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation, indicating that Bmp signaling affects inner-ear development by repressing chsy1. In addition, we obtained strikingly similar zebrafish phenotypes after chsy1 overexpression, which might explain why, in humans, brachydactyly can be caused by mutations leading either to loss or to gain of BMP signaling.

Haplotype frequencies of 17 Y-chromosomal short tandem repeat loci from the Cukurova region of Turkey.

AIM: To investigate the distribution of 17 Y-short tandem repeat (STR) loci in the population of the Cukurova region of Turkey. METHODS: In the period between 2009 and 2010, we investigated the distribution of 17 Y-STRs in a sample of 249 unrelated healthy men from the Cukurova region of Turkey. Genomic DNA was extracted with InstaGene matrix and Y-STRs were determined using the AmpFISTR Yfiler PCR amplification kit. Gene and haplotype diversity values were estimated using the Arlequin software. To compare our data to other populations, population pairwise genetic distances and associated probability values were calculated using the Y Chromosome Haplotype Reference Database Web site software. RESULTS: At 17 Y-STR loci we detected 148 alleles. The lowest gene diversity in this region was 0.51 for DYS391 and the highest 0.95 for DYS385a/b. Haplotype diversity was 0.9997±0.0004. We compared our data with haplotype data of other Turkish populations and no significant differences were found, except with Ankara population (Φst=0.025, P=0.018). Comparisons were also made with the neighboring populations using analysis of molecular variance of the Y-STR loci genetic structure and our population was nearest to Lenkoran-Azerbaijani (Φst=0.012, P=0.068) and Iranian Ahvaz population (Φst=0.007, P=0.173), followed by Greek (Φst=0.025, P=0.000) and Russian (Φst=0.048, P=0.000) population. Other countries like Portugal, Spain, Italy, Egypt, Israel (Palestinian Authority Area), and Taiwan showed a high genetic distance from our population. CONCLUSION: Our study showed that Y-STR polymorphisms were a powerful discrimination tool for routine forensic applications and could be used in genealogical investigations.

Mitochondrial DNA control region haplotype and haplogroup diversity in South Eastern Turkey.

Despite its large geographic and population size only little is known about the mitochondrial (mt)DNA make up of Turkey.orensically relevant data are almost completely absent in the literature. We analyzed the mtDNA control region of 224 volunteers from South Eastern Turkey and compared the data to populations from neighboring countries. The haplotypes will be made available via the EMPOP database (EMP00670) and contribute to the body of forensic mtDNA data.

Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor.

CONTEXT: The neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed within the central nervous system, including hypothalamic nuclei involved in regulating GnRH release. We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). PATIENTS AND METHODS: We sequenced the TACR3 gene in a family in which three siblings had nIHH. The novel mutant receptor thus identified was studied in a heterologous expression system using calcium flux as the functional readout. RESULTS: All affected siblings were homozygous for the His148Leu mutation, in the first extracellular loop of the NKB receptor. The His148Leu mutant receptor exhibited profoundly impaired signaling in response to NKB (EC(50) = 3 +/- 0.1 nm and >5 microm for wild-type and His148Leu, respectively). The location of the mutation in an extracellular part of the receptor led us also to test whether senktide, a synthetic NKB analog, may retain ability to stimulate the mutant receptor. However, the signaling activity of the His148Leu receptor in response to senktide was also severely impaired (EC(50) = 1 +/- 1 nm for wild-type and no significant response of His148Leu to 10 microm). CONCLUSIONS: Homozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. These observations further strengthen the link between NKB, the NKB receptor, and regulation of human reproductive function.