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Genetic analysis of paw usage behavior in the mouse
351
1998 NBTS ABSTRACTS
outcome measures can alter systems mediating ethanol reward. Adapted from NEUROTOXICOL TERATOL 19:391-398, 1996.
NBTS6 LAMMER, E.J., Division of Medical Genetics, Children's Hospital, Oakland, CA. Gene-environment analyses in human birth defects research. Given the suspected etiologic heterogeneity that exists among congenital anomalies, focusing on only environmental, or on only genetic factors, may decrease the likelihood for identifying the contribution of both factors to the risk of common isolated congenital anomalies. Incorporating information on genotypic variation into epidemiological studies of environmental exposures may potentially lead to improvements in case classification, with accompanying improvements in risk estimation. The methodological approaches to analyzing such data are driven by the underlying hypothesis of how the polymorphic variation might influence the relationship of exposure and outcome, and assumptions about whether the variant can act like a "dominant" gene or not. Examples of such research approaches will be presented utilizing data from recent studies of the influence of polymorphic variants of TGF-alpha on maternal smoking and oral cleft risk, and of variants of folate-related genes on maternal multivitamin use and risk ofNTD.
NBTS7 NADEAU J., Genetics Department, Case Western Reserve University, Cleveland Ohio. Strain differences in susceptibility to valproic acid-induced exencephaly in mice. Abstract not received.
NBTS8 BIDDLE, F.G., Departments of Medical Genetics and Medical Biochemistry, University of Calgary, Calgary, Alberta. Genetic analysis of paw usage behavior in the mouse. Paw usage of the mouse in a single-paw reaching task is a simple and reliably measured behavioral trait that exhibits lateral asymmetry. Typically, a mouse is fasted, put into a test chamber with a food tube placed centrally or to the left or right sides and allowed 50 reaches for food. The number of left and right paw reaches is counted; the number (0 to 50) of right paw entries (RPE) provides a measure of direction of lateralit.ation and the number of reaches with the preferred
paw (PPE) provides a measure of strength of lateralization. Experiments will be presented to demonstrate that direction of paw usage depends on genotypically different responses to direction of the test chamber, which leaves a functional imprint on some genotypes. The genetically determined differences among strains is in strength of lateralization, regardless of direction of the test chamber, but the underlying developmental neurobiology is unknown. A threshold mode of liability to be lateralized predicts the distribution of paw usage observed within single genotypes and provides a measure of the differences among genotypes. An F2 analysis between the highly lateralized C57BL/6J and ambilateral CDS/Lay strains suggests an additive genetic model determines the difference in strength of lateralization, with a minimum estimate of five gene loci. A QTL analysis appears to have identified the chromosomal 10cation of one of these genes. The paw usage trait is suggesting clues for the analysis of lateral asymmetry of human handedness. More importantly, it provides an untested model system to explore in behavioral teratology to look for a phenocopy response and genetic differences in the phenocopy response. Supported by the Alberta Children's Hospital Foundation and Medical Research Council of Canada.
NBTS9 ROBERT E., Institut Europeen des Genornutations, Lyon, France. Population-based data on susceptibility to birth defects. Large variations among countries or regions exist in the published evaluations of prevalence at birth of malformations. Besides differences in quality of ascertainment, other factors may explain these variations: exclusion or inclusion of mild forms, exclusion or inclusion of stillbirths, maximum age at diagnosis, access to exploratory methods for diagnosis of internal defects, use of prenatal diagnosis followed by selective abortion of fetuses with severe malformations. These factors may be seen as artefactual sources of variations, and stress that no correct comparison between malformation rates can be performed with data drawn from routine registration. Even when ad hoc studies are conducted, trying to control all definition criteria, strong differences in prevalence are seen, that are likely to reflect differences in the genetic background or in other characteristics of populations. Interactions between genes and environmental factors have been studied more specifically for neural tube defects (NTDs) and oro-facial clefts (OFCs). Population differences in the frequency of some gene alleles, combined especially with dietary patterns or smoking habits of pregnant women, have been explored in the search of the etiology of these anomalies, with contradictory results. On the other hand, long-term time trends exist for some malforma-
1998 NBTS ABSTRACTS
outcome measures can alter systems mediating ethanol reward. Adapted from NEUROTOXICOL TERATOL 19:391-398, 1996.
NBTS6 LAMMER, E.J., Division of Medical Genetics, Children's Hospital, Oakland, CA. Gene-environment analyses in human birth defects research. Given the suspected etiologic heterogeneity that exists among congenital anomalies, focusing on only environmental, or on only genetic factors, may decrease the likelihood for identifying the contribution of both factors to the risk of common isolated congenital anomalies. Incorporating information on genotypic variation into epidemiological studies of environmental exposures may potentially lead to improvements in case classification, with accompanying improvements in risk estimation. The methodological approaches to analyzing such data are driven by the underlying hypothesis of how the polymorphic variation might influence the relationship of exposure and outcome, and assumptions about whether the variant can act like a "dominant" gene or not. Examples of such research approaches will be presented utilizing data from recent studies of the influence of polymorphic variants of TGF-alpha on maternal smoking and oral cleft risk, and of variants of folate-related genes on maternal multivitamin use and risk ofNTD.
NBTS7 NADEAU J., Genetics Department, Case Western Reserve University, Cleveland Ohio. Strain differences in susceptibility to valproic acid-induced exencephaly in mice. Abstract not received.
NBTS8 BIDDLE, F.G., Departments of Medical Genetics and Medical Biochemistry, University of Calgary, Calgary, Alberta. Genetic analysis of paw usage behavior in the mouse. Paw usage of the mouse in a single-paw reaching task is a simple and reliably measured behavioral trait that exhibits lateral asymmetry. Typically, a mouse is fasted, put into a test chamber with a food tube placed centrally or to the left or right sides and allowed 50 reaches for food. The number of left and right paw reaches is counted; the number (0 to 50) of right paw entries (RPE) provides a measure of direction of lateralit.ation and the number of reaches with the preferred
paw (PPE) provides a measure of strength of lateralization. Experiments will be presented to demonstrate that direction of paw usage depends on genotypically different responses to direction of the test chamber, which leaves a functional imprint on some genotypes. The genetically determined differences among strains is in strength of lateralization, regardless of direction of the test chamber, but the underlying developmental neurobiology is unknown. A threshold mode of liability to be lateralized predicts the distribution of paw usage observed within single genotypes and provides a measure of the differences among genotypes. An F2 analysis between the highly lateralized C57BL/6J and ambilateral CDS/Lay strains suggests an additive genetic model determines the difference in strength of lateralization, with a minimum estimate of five gene loci. A QTL analysis appears to have identified the chromosomal 10cation of one of these genes. The paw usage trait is suggesting clues for the analysis of lateral asymmetry of human handedness. More importantly, it provides an untested model system to explore in behavioral teratology to look for a phenocopy response and genetic differences in the phenocopy response. Supported by the Alberta Children's Hospital Foundation and Medical Research Council of Canada.
NBTS9 ROBERT E., Institut Europeen des Genornutations, Lyon, France. Population-based data on susceptibility to birth defects. Large variations among countries or regions exist in the published evaluations of prevalence at birth of malformations. Besides differences in quality of ascertainment, other factors may explain these variations: exclusion or inclusion of mild forms, exclusion or inclusion of stillbirths, maximum age at diagnosis, access to exploratory methods for diagnosis of internal defects, use of prenatal diagnosis followed by selective abortion of fetuses with severe malformations. These factors may be seen as artefactual sources of variations, and stress that no correct comparison between malformation rates can be performed with data drawn from routine registration. Even when ad hoc studies are conducted, trying to control all definition criteria, strong differences in prevalence are seen, that are likely to reflect differences in the genetic background or in other characteristics of populations. Interactions between genes and environmental factors have been studied more specifically for neural tube defects (NTDs) and oro-facial clefts (OFCs). Population differences in the frequency of some gene alleles, combined especially with dietary patterns or smoking habits of pregnant women, have been explored in the search of the etiology of these anomalies, with contradictory results. On the other hand, long-term time trends exist for some malforma-