Non-Mendelian inheritance during inbreeding of Cav3.2 and Cav2.3 deficient mice

The mating of 77 heterozygous pairs (Cav3.2[+|−] x Cav3.2[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups. The mating of 14 pairs (Cav3.2[−|−] female x Cav3.2[+|−] male) and 8 pairs (Cav3.2[+|−] female x Cav3.2[−|−] male) confirmed the significant reduction of deficient homozygous Cav3.2[−|−] pups, leading to the conclusion that prenatal lethality may occur, when one or both alleles, encoding the Cav3.2T-type Ca2+ channel, are missing. Also, the mating of 63 heterozygous pairs (Cav2.3[+|−] x Cav2.3[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups, but only for heterozygous male mice, leading to the conclusion that compensation may only occur for Cav2.3[−|−] male mice lacking both alleles of the R-type Ca2+ channel. During the mating of heterozygous parents, the number of female mice within the weaned population does not deviate from the expected Mendelian inheritance. During prenatal development, both, T- and R-type Ca2+ currents are higher expressed in some tissues than postnatally. It will be discussed that the function of voltage-gated Ca2+ channels during prenatal development must be investigated in more detail, not least to understand devastative diseases like developmental epileptic encephalopathies (DEE).

Somatic Problems and Coping Strategies of Adolescents with Sickle Cell Disease

Out of total sample of the study 72.7 % adolescents were homozygous and 76.7 % were heterozygous. Male and females of Age group 14-16 years were maximum number. Percentage of heterozygous males complaining somatic problems is higher, whereas percentage of homozygous females complaining somatic problems is high. There is significant positive relationship between Maladaptive coping style and somatic problems. Somatic problems emerge as significant predictor in variation of criterion variable somatic problems. The t values explain significant difference in somatic complaints among sickle cell adolescents with respect to gender and zygosity.

DHPLC Scan of Iron Genes in Consecutive Patients with Suspected Iron Overload.

Background: Hereditary Hemochromatosis, once considered a monogenic disorder, is now seen as a polygenic disease, with clinical phenotype also influenced by several environmental factors. Besides the classic HFE gene, other genes involved in modulation of iron homeostasis and clinical phenotype include those coding for hemojuvelin and hepcidin (both responsible for Juvenile Hemochromatosis), ferroportin, and, possibly, H-ferritin. Methods: we used DHPLC to scan mutations in the above mentioned genes in 55 consecutive patients recently referred to our tertiary care unit for iron overload disorders. Many of them had at least biochemical signs of iron overload not explained, or not completely explained, by classic or rare HFE mutations. Main results: the −72 C→T variation in the promoter of hepcidin gene, near the putative TATA box, was found in a H63D heterozygous male with unexplained biochemical signs (serum ferritin 660 μg/L, TS 45%), who, rather, should have been protected by several previous blood donations. We recently found this new hepcidin mutation in a family from another cohort (Biasiotto et al., in press): genotype/phenotype correlation data were also consisting with a functional role of this mutation. Two other hepcidin variations were found in this series, the 108 G→A (new), and the 212 G→A. While the first appeared silent, familial study suggests that the second may be functional in association with C282Y. No new or functional variations were found in hemojuvelin or H-ferritin genes. Several polymorphisms were detected in the ferroportin gene, including two new sequence variations (−116 T→C in the promoter; 691+20C C→T in intron 4), that occurred in two unrelated subjects with wild-type HFE genotype. Their functional role is currently under investigation by extensive family studies and/or quantitative evaluation of hepatic iron by MRI/liver biopsy. Conclusions: DHPLC scan of iron genes appears as a helpful tool for integrating clinical data in selected patients referring for suspected iron overload, as well as for rapid identification of new mutations.

The in vivo and in vitro transmission frequencies of the tw5-haplotype in mice

SummaryThe recessive tω5-haplotype, a complete haplotype, is transmitted by heterozygous male mice at very high frequencies (> 0·90) in normal matings. The present studies were undertaken to determine the effects of delayed matings and in vitro fertilizations on this phenotypic expression. Males carrying the tω5-haplotype ( + / tω5) were first tested for their frequencies of transmission of the mutant 17th chromosome in both normal and delayed matings. Spermatozoa obtained from these same males were then used to fertilize eggs in vitro. The in vivo and in vitro transmission frequencies were found to be statistically equivalent in all types of inseminations. An in vitro fertilization time course study showed that the same percentages of eggs are fertilized by tω5- bearing spermatozoa when the gametes are coincubated for either 2 or 6 h. The data lead to the conclusion that the transmission frequency of the tω5-haplotype is not affected either by the length of time elapsing between insemination and fertilization or by the environment in which fertilization occurs.

Incidence and inheritance of the 1/29 and 14/20 Robertsonian translocations in Canadian beef cattle

Metaphase chromosomes were prepared from peripheral leukocyte cultures of 253 beef animals representing 21 breeds. A total of 10 Robertsonian translocations were identified. Nine were 1/29 fusions and one was a stable 14/20 fusion identified in several Simmentals. To our knowledge, the only other case of this translocation reported was also in the Simmental breed, suggesting that this fusion may be unique to the breed. A further 54 relatives of known 1/29 and 14/20 carriers were examined, revealing that both fusions were inherited by 50% of offspring of the heterozygous carrier. Heterozygous male 1/29 carriers left fewer calves than karyotypically normal bulls when used in natural service. Key words: Robertsonian translocation, cattle, chromosomes, fertility.