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PubMed1999

Preparing for the future: the status of genetics education in diploma-level training courses for nurses in the UK.

This paper offers new information about genetics education provided by diploma level training programmes for nurses in the UK. Those responsible for the development and provision of curricula were asked to complete a questionnaire that attempted to assess the nature of genetics education and their attitudes towards it. The response rate was 84%. Whist genetics teaching is included on all but two training courses, variation in content, delivery and timetable allocation indicates disparity. Genetics is taught for 10 hours or less on most courses, utilizing a limited number of approaches. Most courses do not have compulsory assessment. The majority of respondents (81%) agreed that genetics will have a major impact on health care, and will become an increasingly important issue in education. A small majority (58%) agreed that genetics should have a higher profile in professional training yet many respondents (68%) felt that the teaching they were already offering was appropriate to meet patients' needs. In the absence of any clear national framework for delivery and assessment of genetics education, the author questions whether current training is sufficient to provide nurses with the basic genetic literacy needed to respond to developments in genetics as they impact on health care.

Clinical Competence↗
PubMed1975

Research on variation in dental occlusion. A "state of the art" workshop conducted by the Craniofacial Anomalies Program, the National Institute of Dental Research.

The following report on assessing research on variation in dental occlusion was based in part on a workshop conducted by the National Institute of Dental Research at the initiative of Richard L. Christiansen, Chief, Craniofacial Anomalies Program. The meeting was planned and developed by Robert J. Isaacson, Chairman, Touro M. Graber, Richard A. Riedel, and Richard L. Christiansen. This report is designed to provide a review of the achievements, directions, and needs of research concerning variations in dental occlusion. The workshop was held at the National Institutes of Health, Bethesda, Maryland, on Nov 22 and 23, 1972. The material presented by the workshop participants has been summarized and incorporated in this report. The subject of research related to the field of malocclusion was discussed in an article published in the American Journal of Orthodontics in January, 1971.

Dental Occlusion↗
PubMed2007

Allelic variants in HOX genes in cryptorchidism.

BACKGROUND: Cryptorchidism is one of the most common congenital anomalies and is associated with increased risk for infertility and testicular cancer later in life. Findings from animal models and small clinical studies suggest that the posterior HOX genes (paralogs 9-13) could be potential candidate genes for cryptorchidism and that the HOX genes are functionally redundant within paralogous groups. METHODS: The coding regions and exon-intron boundaries of the 16 posterior HOX genes were sequenced and analyzed in group 1 (44 nonsyndromic cryptorchidism cases and 46 healthy controls). Those specific variants found to be significantly different between cases and controls in group 1 were examined in DNA from group 2 (108 cases and 114 controls). RESULTS: A total of 57 variants was found in group 1, among which the allele frequency of 180A>G (A60A) in HOXD13 alone was significantly elevated in cases versus controls (P = 0.02). In the combined 1 + 2 group, cases were also more likely than controls to have the G allele (P = 0.002). As predicted by an exonic splicing enhancer finder program, the 180A>G (A60A) variant is expected to have an influence on the splicing of transcripts from HOXD13. In group 1, case subjects were more likely to carry multiple variants in HOXA13 and HOXD13 (P = 0.02) than controls. CONCLUSIONS: The variant 180A>G (A60A) in HOXD13 is a risk factor for cryptorchidism, and a dynamic equilibrium of genes in HOX paralog 13 is involved in the pathogenesis of cryptorchidism.

Alleles↗
PubMed1992

HB Al-Ain Abu Dhabi [alpha 18(A16)Gly----Asp]: a new hemoglobin variant discovered in an Emiratee family.

During a routine program of hemoglobin screening performed in the United Arab Emirates, we observed an electrophoretically fast-moving variant in a 9-month-old girl and in several members of her family. The structural determination, performed by reversed phase high performance liquid chromatography and amino acid sequencing, revealed a new variant that we named Hb Al-Ain Abu Dhabi [alpha 18(A16) Gly----Asp]. Its functional properties were normal.

Amino Acid Sequence↗
PubMed2000

Method R estimates of additive genetic, dominance genetic, and permanent environmental fraction of variance for yield and health traits of Holsteins.

Fractions of variance accounted for by additive genetic, dominance genetic, and permanent environmental effects for milk, fat, and protein yields; somatic cell score; and productive life were estimated from Holstein data used for national genetic evaluations. Contemporary group assignments were determined using the national procedure. Data included 1,973,317 milk and fat records for 812,659 cows, 1,019,421 protein records for 462,067 cows, 468,374 lactation average somatic cell score (SCS) records for 232,909 cows, and 735,256 cows with productive-life records. Variance components were estimated with the JAADOM program, which uses iteration on data and second-order Jacobi iteration for obtaining solutions to the mixed-model equations and Method R for estimation of variance components. Ten different random data subsets were used to estimate parameters for each trait. Estimated additive genetic, dominance genetic, and permanent environmental fractions of variance were 0.34, 0.05, and 0.10 for milk yield; 0.34, 0.05, and 0.11 for fat yield; 0.31, 0.05, and 0.10 for protein yield; and 0.17, 0.01, and 0.16 for lactation average SCS. Estimated additive genetic and dominance genetic fractions of variance were 0.12 and 0.06 for productive life. Mean empirical standard errors of additive genetic, dominance genetic, and permanent environmental variance fractions were 0.003, 0.006, and 0.006.

Animals↗
PubMed2026

The First Highly Contiguous Genome Assembly for the Western Bluebird (Sialia mexicana).

The western bluebird (Sialia mexicana) is a secondary cavity-nesting thrush that has experienced historical population declines, local extirpations, and more recent recoveries associated with nest box programs. Despite these regional successes, recent eBird estimates suggest continued range-wide declines and substantial geographic variation in population trajectories, making this species a useful system for future studies of demographic change, connectivity, and conservation genomics. However, genomic resources for western bluebirds remain limited, and no reference genome currently exists for any species in the genus Sialia. Here, we present the first high-quality de novo reference genome for S. mexicana. Using PacBio HiFi long-read sequencing from an adult female, we generated a highly contiguous, phased 1.3 Gb nuclear assembly with a contig N50 of 24.8 Mb and high BUSCO completeness of 98.3%. We annotated the nuclear genome using transcriptomic and protein evidence, identifying 16,656 protein-coding genes and 26,060 transcripts/protein isoforms. We also assembled a complete ∼16 kb mitochondrial genome from Illumina short-read data. This reference genome provides a foundational resource for future studies of population structure, genetic diversity, connectivity, demographic history, and adaptation in western bluebirds and related taxa.

Animals↗
PubMed2004

Genetic recombination between two genotypes of genogroup III bovine noroviruses (BoNVs) and capsid sequence diversity among BoNVs and Nebraska-like bovine enteric caliciviruses.

To determine the genogroups and genotypes of bovine enteric caliciviruses (BECVs) circulating in calves, we determined the complete capsid gene sequences of 21 BECVs. The nucleotide and predicted amino acid sequences were compared phylogenetically with those of known human and animal enteric caliciviruses. Based on these analyses, 15 BECVs belonged to Norovirus genogroup III and genotype 2 (GIII/2) and were genetically distinct from human Norovirus GI and GII. Six BECVs had capsid gene sequences similar to that of the unclassified Nebraska (NB)-like BECV. The 15 bovine noroviruses (BoNVs) were more closely related to Bo/NLV/Newbury-2/76/UK (GIII/2) and other known genotype 2 BoNVs than to genotype 1 Bo/NLV/Jena/80/DE. The BoNV Bo/CV521-OH/02/US showed high nucleotide and amino acid identities (84 and 94%, respectively) with the capsid gene of Bo/NLV/Newbury-2/76/UK, whereas the nucleotide and amino acid sequences of the RNA polymerase gene were more closely related to those of Bo/NLV/Jena/80/DE (77 and 87% identities, respectively) than to those of Bo/NLV/Newbury-2/76/UK (69 and 69% identities, respectively), suggesting that Bo/CV521-OH/02/US is a genotype 1-2 recombinant. Gene conversion analysis by the recombinant identification program and SimPlot also predicted that Bo/CV521-OH/02/US was a recombinant. Six NB-like BECVs shared 88 to 92% nucleotide and 94 to 99.5% amino acid identities with the NB BECV in the capsid gene. The results of this study demonstrate genetic diversity in the capsid genes of BECVs circulating in Ohio veal calves, provide new data for coinfections with distinct BECV genotypes or genogroups, and describe the first natural BoNV genotype 1-2 recombinant, analogous to the previously reported human norovirus recombinants.

Animals↗
PubMed2006

Searching for polymorphisms that affect gene expression and mRNA processing: example ABCB1 (MDR1).

Cis-acting genetic variations can affect the amount and structure of mRNA/protein. Genomic surveys indicate that polymorphisms affecting transcription and mRNA processing, including splicing and turnover, may account for the main share of genetic factors in human phenotypic variability; however, most of these polymorphisms remain yet to be discovered. We use allelic expression imbalance (AEI) as a quantitative phenotype in the search for functional cis-acting polymorphisms in many genes, including ABCB1 (multidrug resistance 1 gene, MDR1, Pgp). Previous studies have shown that ABCB1 activity correlates with a synonymous polymorphism, C3435T; however, the functional polymorphism and molecular mechanism underlying this clinical association remained unknown. Analysis of allele-specific expression in liver autopsy samples and in vitro expression experiments showed that C3435T represents a main functional polymorphism, accounting for 1.5- to 2-fold changes in mRNA levels. The mechanism appears to involve increased mRNA turnover, probably as a result of different folding structures calculated for mRNA with the Mfold program. Other examples of the successful application of AEI analysis for studying functional polymorphism include 5-HTT (serotonin transporter, SLC6A4) and OPRM1 (mu opioid receptor). AEI is therefore a powerful approach for detecting cis-acting polymorphisms affecting gene expression and mRNA processing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Miglustat (NB-DNJ) works as a chaperone for mutated acid beta-glucosidase in cells transfected with several Gaucher disease mutations.

Gaucher disease (GD) is a disorder of glycosphinglipid metabolism caused by deficiency of lysosomal acid beta-glucosidase (GC), resulting in progressive deposition of glucosylceramide in macrophages. The glucose analogue, N-butyl-deoxynojirimycin (NB-DNJ, Miglustat), is an inhibitor of the ceramide-specific glucosyltransferase (CSG) which catalyzes the first step of glycosphingolipids biosynthesis and is currently approved for the oral treatment of type 1 GD. Using site-directed mutagenesis, we constructed plasmids containing wild-type and several mutations in glucocerebrosidase (GBA) gene. The plasmids were transfected into COS-7 cells and stable transfected cell lines were obtained by geneticin (G418) selection. Cells were cultured during 6 days with medium with or without 10 microM NB-DNJ. The addition of NB-DNJ to COS-7 cell medium leads to 1.3-, 2.1-, 2.3-, 3.6-, and 9.9-fold increase in the activity of S364R, wild-type, N370S, V15M, and M123T GC, respectively. However, no significant changes were observed in the activity of the L444P, L336P, and S465del mutated proteins, but a small decrease in the rare P266L variant was observed. These results suggest that NB-DNJ, in addition to the inhibitory effect on CSG, also works as a "chemical chaperone", increasing the activity of acid beta-glucosidase of wild-type and several GC mutated proteins, including the most frequent N370S mutation. The specific location of the Miglustat binding site in GC is unknown. Potential binding sites in the enzyme have been searched for using computational molecular docking. The searching strategy identified three potential GC binding sites for Miglustat, one being the substrate-binding site of the enzyme, which was the best-ranked site by AutoDock program. Therefore, it is possible that Miglustat exerts its chaperoning activity on acid beta-glucosidase by acting as an inhibitor bound at the active site. This increase on the activity of the acid beta-glucosidase would imply that Miglustat is not only a substrate reducer but also an inhibitor of the GC degradation, with very promising clinical implications for the treatment of GD patients.

1-Deoxynojirimycin↗
PubMed1992

Gynaecologists' abortion practice.

OBJECTIVE: To ascertain the relation between gynaecologists' opinions on the provision of abortion and the service provided by the Health Service in their district and to investigate the methods used for second trimester abortion. DESIGN AND SETTING: A postal questionnaire sent three times to a 50% random sample of gynaecologists practising in the National Health Service (NHS) in 1989 in Great Britain. SUBJECTS: 343 of 396 practising gynaecologists, 87% of those selected. MAIN OUTCOME MEASURES: Proportion of gynaecologists holding views or reporting practice. RESULTS: Although only 11% actually performed abortions beyond 20 weeks, 57% approved later operations in cases of rape and 85% for a threat to the woman's health; only 47% approved late abortion for schoolgirls under 16 years. Dilatation and evacuation was used by only 1% of NHS gynaecologists even though from 13 to 16 weeks it is a safe and efficient method. Although Government statistics report that vacuum aspiration is used in over one third of second trimester abortions, this is technically unlikely and was not confirmed by this study. Less than 50% of abortions in England and Wales are performed in the NHS yet fewer than 40% of gynaecologists reported problems in providing an abortion service. Overall 21% thought they were providing abortions for over 90% of the women resident in their districts, whereas only 2% of districts achieve this proportion in their home regional health authority. Overall 60% supported separating abortion work from general gynaecology, and 45% would like regional abortion units. Only 27% supported fertility control acquiring the status of a subspecialty. CONCLUSIONS: Accepting these suggestions would improve the service, reduce regional variations in provision, provide opportunities for research and could have an important effect in helping slow the world population increase.

Abortion, Therapeutic↗
PubMed2005

SNPsFinder--a web-based application for genome-wide discovery of single nucleotide polymorphisms in microbial genomes.

UNLABELLED: Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic variations in closely related microbial species, strains or isolates. Some SNPs confer selective advantages for microbial pathogens during infection and many others are powerful genetic markers for distinguishing closely related strains or isolates that could not be distinguished otherwise. To facilitate SNP discovery in microbial genomes, we have developed a web-based application, SNPsFinder, for genome-wide identification of SNPs. SNPsFinder takes multiple genome sequences as input to identify SNPs within homologous regions. It can also take contig sequences and sequence quality scores from ongoing sequencing projects for SNP prediction. SNPsFinder will use genome sequence annotation if available and map the predicted SNP regions to known genes or regions to assist further evaluation of the predicted SNPs for their functional significance. SNPsFinder can generate PCR primers for all predicted SNP regions according to user's input parameters to facilitate experimental validation. The results from SNPsFinder analysis are accessible through the World Wide Web. AVAILABILITY: The SNPsFinder program is available at http://snpsfinder.lanl.gov/. SUPPLEMENTARY INFORMATION: The user's manual is available at http://snpsfinder.lanl.gov/UsersManual/

Algorithms↗
PubMed2005

Genetic diversity of the dengue vector Aedes aegypti in Australia and implications for future surveillance and mainland incursion monitoring.

In February 2004, the discovery of an incursion of the dengue vector Aedes aegypti into the town of Tennant Creek in the Northern Territory caused concern for the Northern Territory health authorities who proceeded to implement a Commonwealth-funded eradication program. To determine the origin of the incursion, we performed a genetic analysis on Ae. aegypti from several Queensland and overseas localities. A comparison of DNA sequences from the mitochondrial cytochrome oxidase 1 gene indicated that the incursion was probably from Cairns or Camooweal. This genetic marker was also useful in identifying a separate Townsville haplotype population and another population on Thursday Island in the Torres Strait that was genetically divergent to the mainland populations. The possible use of this marker as a surveillance tool for identifying the origins of local and overseas incursions is discussed.

Aedes↗
PubMed1986

A new method for DNA surface-property display and its application to E. coli promoter sequences.

A personal computer program to visualize and compare the property of double-stranded DNA surface has been developed. Comparison of the surface property between Watson-Crick base-pairs in B-form DNA has elucidated that the base-pair replacement between a "degenerated base-pairs" conserves the pattern of potential hydrogen-bonding sites in both major and minor grooves. The idea of the "degenerated base-pairs" was applied for the problem of the base-sequence variation from the consensus sequence in the -35 region of E. coli promoter. The sequence variation is found to have tendency to occur among the degenerated base-pairs.

Computer Graphics↗
PubMed1998

Accuracy of ultrasonic pachymetry and videokeratography in detecting keratoconus.

PURPOSE: To compare the accuracy of ultrasonic pachymetry measurements and videokeratography-derived indices in distinguishing keratoconus patients from those with normal eyes. SETTING: A subspecialty cornea practice (Los Angeles, California, USA) and the Keratoconus Genetics Research Project. METHODS: Corneal thickness was measured by ultrasonic pachymetry at the center and inferior margins of the pupil of 142 normal and 99 keratoconus patients The corneal surface topography of patients was studied with the Topographic Modeling System (TMS-1). The videokeratographs obtained were analyzed with a computer program that automatically calculates two indices derived from data points in the central and paracentral cornea: central K and I-S values. Linear discriminant analysis was used to determine the correct classification percentages using pachymetry measurements and indices derived from videokeratography as the independent variables. RESULTS: The range of corneal thickness in normal and keratoconic eyes overlapped considerably. In the discriminant analysis, videokeratography indices provided a 97.5% correct classification rate and pachymetry data, an 86.0% rate (P < .01, McNemar's test). CONCLUSION: Keratoconus is more accurately distinguished from the normal population by videokeratography-derived indices than by ultrasonic pachymetry measurements. This may be due to the large variation in corneal thickness in the normal population or the inability of ultrasonic pachymetry to accurately detect the location of corneal thinning in keratoconus by measuring standard points on the cornea. Pachymetry should not be relied on to exclude or diagnose keratoconus because the false-negative and false-positive rates are unacceptably higher than those obtained by videokeratography.

Cornea↗
PubMed2003

Segmentation: mono- or polyphyletic?

Understanding the evolutionary origins of segmented body plans in the metazoa has been a long-standing fascination for scientists. Competing hypotheses explaining the presence of distinct segmented taxa range from the suggestion that all segmentation in the metazoa is homologous to the proposal that segmentation arose independently many times, even within an individual clade or species. A major new source of information regarding the extent of homology vs. homoplasy of segmentation in recent years has been an examination of the extent to which molecular mechanisms underlying the segmentation process are conserved, the rationale being that a shared history will be apparent by the presence of common molecular components of a developmental program that give rise to a segmented body plan. There has been substantial progress recently in understanding the molecular mechanisms underlying the segmentation process in many groups, specifically within the three overtly segmented phyla: Annelida, Arthropoda and Chordata. This review will discuss what we currently know about the segmentation process in each group and how our understanding of the development of segmented structures in distinct taxa have influenced the hypotheses explaining the presence of a segmented body plan in the metazoa.

Animals↗
PubMed2004

Serial SimCoal: a population genetics model for data from multiple populations and points in time.

UNLABELLED: We present Serial SimCoal, a program that models population genetic data from multiple time points, as with ancient DNA data. An extension of SIMCOAL, it also allows simultaneous modeling of complex demographic histories, and migration between multiple populations. Further, we incorporate a statistical package to calculate relevant summary statistics, which, for the first time allows users to investigate the statistical power provided by, conduct hypothesis-testing with, and explore sample size limitations of ancient DNA data. AVAILABILITY: Source code and Windows/Mac executables at http://www.stanford.edu/group/hadlylab/ssc.html CONTACT: senka@stanford.edu.

Biological Evolution↗
PubMed2005

ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women.

The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

Actinin↗
PubMed1990

Androgyne becomes bisexual in sexological theory: Plato to Freud and neuroscience.

Plato conceptualized primordial humans as androgynes, the children of the moon. The primordial hermaphroditism of the mammalian embryo became known 2 1/2 millennia later in the mid-19th century. By 1864 Ulrichs had transposed the new knowledge from embryology to sexology to explain those to whom he gave the name Urnings (after Uranus who gave womanless birth to Venus from sea spume) as having "a woman's mind trapped in a man's body" (anima muliebris corpore virili inclusa). Urning became displaced by sexual inversion, and eventually by homosexual, a term coined together with heterosexual by Kertbeny as recently as 1869. The embryological principle of primordial hermaphroditism became linked to evolutionary Darwinism by way of Haeckel's principle of recapitulation, epitomized as "ontogeny recapitulates phylogeny." The recapitulation principle became linked, in turn, to the principle of intrapsychic primordial bisexuality, which became a cornerstone of Freud's psychoanalytic theory. Genetics influences the outcome of bipotentiality not directly but by way of hormonal programming of the brain, prenatally or neonatally, rather than pubertally and in maturity. Bipotentiality within the brain has been investigated chiefly in the hypothalamus where male/female dimorphism has been recognized, but its determinants and stages of differentiation, both prenatal and postnatal, remain to be fully ascertained. Neuroanatomical research on the outcome of male/female bipotentiality as gay, straight, or in between is politically and morally opposed by those who postulate a bipotential preference or voluntary choice. In stimulus-response associationism, to which behavior-modification theory belongs, bisexuality is equipotential, and either alternative may be evoked, ostensibly, dependent on the stimulus situation. In ethological theory, the effectiveness of stimulus-response bonding is confined chronologically to a critical period of development and is restricted phylogenetically by an innate recognition mechanism and an innate releasing mechanism. These limits are compatible, however, with some degree of both individual and ethnic variation.

Bisexuality↗