The homeotic genespineless-aristapedia affects geotaxis inDrosophila melanogaster

The homeotic mutationspineless-aristapedia (ss ^a ) transforms the aristae into second tarsi. Flies with aSS ^a phenotype also show extremely positive geotaxis as measured in a Hirsch-type geotaxis maze. Other antennal mutants and flies with their aristae amputated do not show such extreme positive geotaxis. Deletion analysis has comapped the geotaxis effect withSS ^a in band 89C on the third chromosome. Finally, a biometrical analysis has detected additional genes on the X chromosome that also affects geotaxis.This work was supported by a Charles and Johanna Busch Memorial Award to T.R.M. and an Anne B. and James H. Leathem Scholarship Fund Award to P.A.M.Department of Biological Sciences and Bureau of Biological Research, Nelson Biological Laboratories     

Novel germline BRCA1 and BRCA2 mutations in breast and breast/ovarian cancer families from the Czech Republic

Germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for a substantial proportion of high‐risk breast and breast/ovarian cancer families. To characterize the spectrum of BRCA1 and BRCA2 mutations, we screened Czech families with breast/ovarian cancer using the non‐radioactive protein truncation test, heteroduplex analysis and direct sequencing. In a group of 100 high‐risk breast and breast/ovarian cancer families, four novel frame shift mutations were identified in BRCA1 and BRCA2 genes. In BRCA1, two novel frame shift mutations were identified as 3761‐3762delGA and 2616‐2617ins10; in BRCA2, two novel frame shift mutations were identified as 5073‐5074delCT and 6866delC. Furthermore, a novel missense substitution M18K in BRCA1 gene in a breast/ovarian cancer family was identified which lies adjacent just upstream of the most highly conserved C3HC4 RING zinc finger motif. To examine the tertiary structure of the RING zinc finger domain and possible effects of M18K substitution on its stability, we used threading techniques according to the crystal structure of RAG1 dimerization domain of the DNA‐binding protein. © 2000 Wiley‐Liss, Inc.     

Physical separation of HLA-A alleles by denaturing high-performance liquid chromatography

Genomic typing of polymorphic loci may be hampered by ambiguous typing results. Moreover, robust methods for simultaneous sequencing of two alleles present in a given sample may be difficult to establish. We used denaturing high-performance liquid chromatography (DHPLC) for physical separation of HLA-A alleles before sequence-based genomic typing (SBT). Physical separation was achieved by resolution of heteroduplexes between the sample alleles and a modified reference probe by DHPLC followed by selective reamplification of the sample alleles present in heteroduplexes. Complementary strands of the reference probe and sample alleles for heteroduplex induction were obtained by lambda-exonuclease digestion. HLA-A genotyping of 101 individuals using DHPLC-SBT yielded better typing resolution compared with serological typing and genotyping by the sequence-specific primer-polymerase chain reaction (SSP-PCR) method. Physical separation of alleles using a modified reference probe allows for development of fully automated methods for genomic typing of highly polymorphic loci such as HLA.     

Heredity-environment analyses of Jencks's IQ correlations

Three different published heredity-environment analyses of Jencks's summary correlations for IQ have yielded strikingly different results. It is shown empirically that differences in selection of data and in computational procedures and logical inconsistencies in specifying equations are not responsible for the differences in results. Rather, the differences trace to the underlying assumptions made by the various authors. The analyses suggest that the assumptions concerning genetic dominance, assortative mating, and special twin environments were especially critical, while those regarding selective placement and different modes of environmental transmission were not.     

Publication Guidelines for Heart Rate Studies in Man

Publication guidelines are provided for the collection, quantification, and analysis of heart rate data.     

Molecular typing of echovirus serotype 4 isolates

We report on clinical samples Stuttgart/97, Berlin/99 and Jasi/99 associated with aseptic meningitis. All three samples contained echovirus 4 (E4) but Stuttgart/97 was simultaneous infected with echovirus 30 (E30). The genetic relationship of the E4 strains was assessed using RT-PCR and direct sequencing of amplicons derived from the genomic region encoding the capsid protein VP1. The sequences have been compared with each other and with sequences of further E4 strains obtained from GenBank. The analysis confirms that sequences of recent isolates have drifted away from elderly strains over a longer period of time. Several amino acid changes in assumed antigenic sites of the VP1 gene may be sufficient to cause changes in antigenic specificity and therefore they may be a reason for failure of serological typing of some new antigenic E4 variants.     

Identification of the novel allele HLA-DRB1*1137 which probably originated from DRB1*11011: implications for mismatch with its ancestor allele at bone marrow transplantation

The identification of the new allele HLA-DRB1*1137, which was found in a Caucasian individual, is described. In the sequence analysis the new allele differs from DRB1*11011 by position 227 (T>A) which is located in exon 2. At the protein level, the new allele has one amino acid difference compared to DRB1*1101 (Phe47Tyr). Residue 47 is likely to contribute to the peptide binding site of HLA-DR11 and thus to be important for peptide binding. However, as phenylalanine and tyrosine have very similar physical and chemical features allogenicity in case of mismatch at bone marrow transplantation may be weak.     

Impaired postural compensation for respiration in people with recurrent low back pain

This study evaluated the degree to which the disturbance to posture from respiration is compensated for in healthy normals and whether this is different in people with recurrent low back pain (LBP), and to compare the changes when respiratory demand is increased. Angular displacement of the lumbar spine and hips, and motion of the centre of pressure (COP), were recorded with high resolution and respiratory phase was recorded from ribcage motion. With subjects standing in a relaxed posture, recordings were made during quiet breathing, while breathing with increased dead-space to induce hypercapnoea, and while subjects voluntarily increased their respiration to match ribcage expansion that was induced in the hypercapnoea condition. The relationship between respiration and the movement parameters was measured from the coherence between breathing and COP and angular motion at the frequency of respiration, and from averages triggered from the respiratory data. Small angular changes in the lumbopelvic and hip angles were evident at the frequency of respiration in both groups. However, in quiet standing, the LBP subjects had a greater displacement of their COP that was associated with respiration than the control subjects. The LBP group had a trend for less hip motion. There were no changes in the movement parameters when respiratory demand increased involuntarily via hypercapnoea, but when respiration increased voluntarily, the amplitude of motion and the displacement of the COP increased in both groups. The present data suggest that the postural compensation to respiration counteracts at least part of the disturbance to posture caused by respiration and that this compensation may be less effective in people with LBP.     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.