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Biomedical subjects

M G Turri

Publications and source records attributed to M G Turri.

6 recordsLinked to original sources
PubMed2001

QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice.

BACKGROUND: Ethological tests of anxiety-related behaviors, such as the open field arena and elevated plus maze, are often carried out on transgenic animals in the attempt to correlate gene function with a behavioral phenotype. However, the interpretation of such tests is problematic, as it is probable that different tests measure different aspects of behavior; indeed, anxiety may not be a unitary phenomenon. Here, we address these questions by asking whether behaviors in five ethological tests of anxiety are under the influence of a common set of genes. RESULTS: Using over 1600 F2 intercross animals, we demonstrate that separate, but overlapping, genetic effects can be detected that influence different behavioral dimensions in the open field, elevated plus maze, square maze, light-dark box, and mirror chamber. We find quantitative trait loci (QTLs) on chromosomes 1, 4, and 15 that operate in four tests of anxiety but can be differentiated by their action on behavior in threatening and nonthreatening environments and by whether habituation of the animals to an aversive environment alters their influence. QTLs on chromosomes 7, 12, 14, 18, and X influenced a subset of behavioral measures. CONCLUSIONS: The chromosome 15 QTL acts primarily on avoidance behavior, the chromosome 1 QTL influences exploration, and the QTL on chromosome 4 influences activity. However, the effects of loci on other chromosomes are not so readily reconciled with our current understanding of the psychology of anxiety. Genetic effects on behaviors in these tests are more complex than expected and may not reflect an influence on anxiety.

Animals↗
PubMed2001

Automatic analysis of agarose gel images.

MOTIVATION: Automatic tools to speed up routine biological processes are very much sought after in bio-medical research. Much repetitive work in molecular biology, such as allele calling in genetic analysis, can be made semi-automatic or task specific automatic by using existing techniques from computer science and signal processing. Computerized analysis is reproducible and avoids various forms of human error. Semi-automatic techniques with an interactive check on the results speed up the analysis and reduce the error. RESULTS: We have successfully implemented an image processing software package to automatically analyze agarose gel images of polymorphic DNA markers. We have obtained up to 90% accuracy for the classification of alleles in good quality images and up to 70% accuracy in average quality images. These results are obtained within a few seconds. Even after subsequent interactive checking to increase the accuracy of allele classification to 100%, the overall speed with which the data can be processed is greatly increased, compared to manual allele classification. AVAILABILITY: The IDL source code of the software is available on request from jonathan.flint@well.ox.ac.uk

Animals↗
PubMed2001

Quantitative trait locus mapping in laboratory mice derived from a replicated selection experiment for open-field activity.

Bidirectional selection in rodents has been used to derive animal models of human behavior. An important question is whether selection for behavior operates on a limited number of QTL or whether the number and individual contribution of QTL varies between selection experiments. To address this question, we mapped QTL in two large F2 intercrosses (N = 815 and 821) from the four lines derived from a replicated selection experiment for open-field activity, an animal model for susceptibility to anxiety. Our analyses indicate that selection operated on the same relatively small number of loci in both crosses. Haplotype information and the direction of effect of each QTL allele were used to confirm that the QTL mapped in the two crosses lie in the same chromosomal regions, although we were unable to determine whether QTL in the two crosses represent the same genes. We conclude that the genetic architecture of the selected strains is similar and relatively simple.

Animals↗
PubMed2000

A method for fine mapping quantitative trait loci in outbred animal stocks.

High-resolution mapping of quantitative trait loci (QTL) in animals has proved to be difficult because the large effect sizes detected in crosses between inbred strains are often caused by numerous linked QTLs, each of small effect. In a study of fearfulness in mice, we have shown it is possible to fine map small-effect QTLs in a genetically heterogeneous stock (HS). This strategy is a powerful general method of fine mapping QTLs, provided QTLs detected in crosses between inbred strains that formed the HS can be reliably detected in the HS. We show here that single-marker association analysis identifies only two of five QTLs expected to be segregating in the HS and apparently limits the strategy's usefulness for fine mapping. We solve this problem with a multipoint analysis that assigns the probability that an allele descends from each progenitor in the HS. The analysis does not use pedigrees but instead requires information about the HS founder haplotypes. With this method we mapped all three previously undetected loci [chromosome (Chr.) 1 logP 4.9, Chr. 10 logP 6.0, Chr. 15 logP 4.0]. We show that the reason for the failure of single-marker association to detect QTLs is its inability to distinguish opposing phenotypic effects when they occur on the same marker allele. We have developed a robust method of fine mapping QTLs in genetically heterogeneous animals and suggest it is now cost effective to undertake genomewide high-resolution analysis of complex traits in parallel on the same set of mice.

Animals↗
PubMed1995

Characterisation of a novel minisatellite that provides multiple splice donor sites in an interferon-induced transcript.

Nucleotide sequence features of the human interferon-inducible gene 6-16 are described and include, within a CpG island, a partially expressed minisatellite consisting of 26 tandemly repeated dodecanucleotides. The repeat unit consensus sequence (CAGGTAAGGGTG) is similar to the mammalian splice donor consensus sequence [(A/C)AGGT(A/G)AGT]. The splice donor site of exon 2, as determined previously, forms part of the most upstream of the repeat units. We show that the two neighbouring repeat units also provide functional splice donor sites effectively extending exon 2 by 12 or 24 nt and inserting four or eight amino acids respectively into the predicted gene product. A similar pattern of differently spliced transcripts is detected in several human cell types. Both the number of repeat units per allele and the nucleotide sequence itself show limited polymorphism within the human population. Similar minisatellites from nonhuman primates are described and also appear to modulate splicing of a 6-16 transcript. The 6-16 minisatellite is therefore an example of tandemly repeated DNA that has a role in gene expression and may provide a useful in vivo system for the analysis of 5' splice site choice and minisatellite biology.

Amino Acid Sequence↗