Biomedical subjects

L L Janss

Publications and source records attributed to L L Janss.

14 recordsLinked to original sources

PubMed2001

Heritability estimations for diseases, coat color, body weight, and height in a birth cohort of Boxers.

OBJECTIVE: To obtain heritability estimates for diseases and characteristics in Boxers. ANIMALS: Birth cohort of 2,929 purebred Boxers from 414 litters. PROCEDURE: Heritability estimates were determined for cheiloschisis-palatoschisis, cryptorchidism, epilepsy, stifle disorders, cardiac disorders, coat color, birth weight, and adult weight, and height. Binary traits were analyzed by use of a mixed-effects probit model. Some traits also were analyzed by use of a model that postulated monogenic inheritance. Full pedigree analyses were performed. Variation in incidences of disease among clusters of related dogs was evaluated. RESULTS: Heritability estimates were virtually zero for cardiac disorders, medium (0.17 to 0.36) for most other traits, and high (> 0.55) for coat color, birth weight, and adult height. Litter effects and risk factors affected cheiloschisis-palatoschisis, heart murmur, coat color, broadly defined epilepsy, and adult weight. Litter effects may be attributable to common environmental effects for littermates but also may be attributable to dominance variation caused by a recessive gene. Heritability estimates increased when stricter definitions for epilepsy and stifle disorders were used. The monogenic model did not reveal higher heritability estimates for 6 traits analyzed. Incidences for white coat differed significantly for 10 familial clusters, confirming high heritability and effects of familial lineage. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that genetic improvement of most traits should be feasible, except for cardiac disorders. However, because most traits are influenced by environmental effects as well as genetic effects, genetic counseling based on polygenic inheritance and use of familial information rather than strict exclusion of parents is preferred.

Animals↗

PubMed2001

Disease-induced variability of genetic correlations: ascites in broilers as a case study.

Breeding against a production disease is complicated by multiple relationships between productivity, disease, and environment. Ascites in broilers is such a disease. The combination of the reasonably well understood etiology (a physiological/pathological cascade due to inadequate oxygen supply) and the practical relevance makes ascites a relevant case for demonstrating and partly revealing these complex relationships. Chickens (n = 2,788) were tested in an ascites-challenging (cold) environment. Genetic analysis of mortality and pathology in combination with performance and physiological traits (especially blood gas traits) revealed ample opportunities for selection against ascites expression. The genetic correlation structure indicated that different mortality traits and pathology traits roughly represent one common characteristic. Direct selection against pathology is more effective than selection on the basis of growth or blood gas traits. The observed negative correlation (-0.26) between productivity and ascites was unexpected. From the etiology of ascites (inadequate supply of oxygen relative to the demand), a positive (unfavorable) correlation was expected. To demonstrate that the actual disease occurrence caused this apparent contradiction, the data from the undiseased subpopulation were reanalyzed. In the undiseased subpopulation, the genetic correlation between productivity and ascites was positive (0.29). This discrepancy was confirmed by comparing regression of ascites expression on actual performance with regression of ascites on independently assessed performance breeding values. The lability of the genetic correlation was explained from complex interactions between productivity, disease susceptibility, and actual occurrence of the disease. The revealed mechanism can be generalized to other production-related diseases and results in systematically lower genetic correlations between disease and productivity. It was inferred that genetic correlations between productivity and such diseases will always be prone to the demonstrated environmental sensitivity, which complicates index selection against production-related diseases.

Animals↗

PubMed2000

Power of quantitative trait locus mapping for polygenic binary traits using generalized and regression interval mapping in multi-family half-sib designs.

A generalized interval mapping (GIM) method to map quantitative trait loci (QTL) for binary polygenic traits in a multi-family half-sib design is developed based on threshold theory and implemented using a Newton-Raphson algorithm. Statistical power and bias of QTL mapping for binary traits by GIM is compared with linear regression interval mapping (RIM) using simulation. Data on 20 paternal half-sib families were simulated with two genetic markers that bracketed an additive QTL. Data simulated and analysed were: (1) data on the underlying normally distributed liability (NDL) scale, (2) binary data created by truncating NDL data based on three thresholds yielding data sets with three different incidences, and (3) NDL data with polygenic and QTL effects reduced by a proportion equal to the ratio of the heritabilities on the binary versus NDL scale (reduced-NDL). Binary data were simulated with and without systematic environmental (herd) effects in an unbalanced design. GIM and RIM gave similar power to detect the QTL and similar estimates of QTL location, effects and variances. Presence of fixed effects caused differences in bias between RIM and GIM, where GIM showed smaller bias which was affected less by incidence. The original NDL data had higher power and lower bias in QTL parameter estimates than binary and reduced-NDL data. RIM for reduced-NDL and binary data gave similar power and estimates of QTL parameters, indicating that the impact of the binary nature of data on QTL analysis is equivalent to its impact on heritability.

Algorithms↗

PubMed2000

A transmission/disequilibrium test approach to screen for quantitative trait loci in two selected lines of large white pigs.

Pedigree and marker data from a multiple-generation pig selection experiment have been analysed to screen for loci affecting quantitative traits (QTL). Pigs from a base population were selected either for low backfat thickness at fixed live weight (L-line) or high live weight at fixed age (F-line). Selection was based on single-trait own performance and DNA was available on selected individuals only. Genotypes for three marker loci with known positions on chromosome 4 were available. The transmission/disequilibrium test (TDT) was originally described in human genetics to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Here, we adapt the TDT to test for linkage between a marker and QTL favoured by selection, and for linkage disequilibrium between them in the base population. The a priori unknown distribution of the test statistic under the null hypothesis, no linkage, was obtained via Monte Carlo simulation. Significant TDT statistics were found for markers AFABP and SW818 in the F-line, indicating the presence of a closely linked QTL affecting growth performance. In the L-line, none of the markers studied showed significance. This study emphasizes the potential of the TDT as a quick and simple approach to screen for QTL in situations where marker genotypes are available on selected individuals. The results suggest that previously identified QTL in crosses of genetically diverse breeds may also segregate in commercial selection lines.

Animals↗

PubMed2000

Markov chain Monte Carlo for mapping a quantitative trait locus in outbred populations.

A Bayesian approach is presented for mapping a quantitative trait locus (QTL) using the 'Fernando and Grossman' multivariate Normal approximation to QTL inheritance. For this model, a Bayesian implementation that includes QTL position is problematic because standard Markov chain Monte Carlo (MCMC) algorithms do not mix, i.e. the QTL position gets stuck in one marker interval. This is because of the dependence of the covariance structure for the QTL effects on the adjacent markers and may be typical of the 'Fernando and Grossman' model. A relatively new MCMC technique, simulated tempering, allows mixing and so makes possible inferences about QTL position based on marginal posterior probabilities. The model was implemented for estimating variance ratios and QTL position using a continuous grid of allowed positions and was applied to simulated data of a standard granddaughter design. The results showed a smooth mixing of QTL position after implementation of the simulated tempering sampler. In this implementation, map distance between QTL and its flanking markers was artificially stretched to reduce the dependence of markers and covariance. The method generalizes easily to more complicated applications and can ultimately contribute to QTL mapping in complex, heterogeneous, human, animal or plant populations.

Animals↗

PubMed2000

The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs.

Effects of genetic variation in porcine adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, respectively, on intramuscular fat (IMF) content and backfat thickness (BFT) were examined in F2 crossbreds of Meishan and Western pigs. The involvement of each FABP gene in IMF accretion was studied to confirm previous results for Duroc pigs. The F2 crossbred pigs were genotyped for various markers including microsatellite sequences situated within both FABP genes. Linkage analysis assigned the A-FABP and H-FABP genes to marker intervals S0001-S0217 (20 cM) on SSC4 and Sw316-S0003 (16.6 cM) on SSC6, respectively, refining previous chromosomal assignments. Next, the role of both chromosome regions/genes on genetic variation in IMF content and BFT was studied by 1) screening SSC4 and SSC6 for QTL affecting both traits by performing a line-cross analysis and 2) estimation of the effect of individual A-FABP and H-FABP alleles on both traits. In the first analysis, suggestive and chromosome-wise significant evidence for a QTL affecting IMF was detected on SSC6. The H-FABP gene is a candidate gene for this effect because it resides within the large region containing this putative QTL. The second analysis showed a considerable but nonsignificant effect of H-FABP microsatellite alleles on IMF content. Suggestive evidence for a QTL affecting BFT was found on SSC6, but H-FABP was excluded as a candidate gene. In conclusion, present and previous results support involvement of H-FABP gene polymorphisms in IMF accretion independently from BFT in pigs. Therefore, implementation of these polymorphisms in marker-assisted selection to control IMF content independently from BFT may be considered. In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population.

Adipocytes↗

PubMed2000

Heritabilities of and genetic relationships between salmonella resistance traits in broilers.

Using experimental infections, three traits for salmonella resistance were studied: mortality, survival time (in animals that died by infection), and quantitative cecal salmonella carriage at the end of the rearing period (in animals that did not die). In total, 548 animals were used; mortality was 29.2%, mean survival time was 5.97 d (n = 160), and the mean 10log of colony forming units per gram of cecal contents was 1.62 (n = 387). Genetic parameters were evaluated in bivariate threshold-linear models to account for the selective measurement of survival time and cecal carriage. Heritabilities were .06 for survival time, .09 for cecal carriage, and .12 for mortality. The genetic correlation between mortality and cecal carriage was weak (.26), which suggests that these traits are largely controlled by different genes. The genetic correlation between mortality and survival time was relatively strong (-.68). Simultaneous study of multiple traits seems to be of particular importance in judging epidemiological consequences of a possible selection for resistance. Results here indicate that selection on decreased mortality could be unfavorable for the spread of salmonella because the resulting correlated increase in survival time, implying longer shedding by infected animals, is relatively stronger than the correlated decrease in level of cecal carriage. Selection to reduce the level of cecal salmonella carriage could be done while keeping survival time constant, if so desired, because the correlation between these traits is weak (-.15).

Animals↗

PubMed2000

Genetic parameters of legendre polynomials for first parity lactation curves.

Variance components of the covariance function coefficients in a random regression test-day model were estimated by Legendre polynomials up to a fifth order for first-parity records of Dutch dairy cows using Gibbs sampling. Two Legendre polynomials of equal order were used to model the random part of the lactation curve, one for the genetic component and one for permanent environment. Test-day records from cows registered between 1990 to 1996 and collected by regular milk recording were available. For the data set, 23,700 complete lactations were selected from 475 herds sired by 262 sires. Because the application of a random regression model is limited by computing capacity, we investigated the minimum order needed to fit the variance structure in the data sufficiently. Predictions of genetic and permanent environmental variance structures were compared with bivariate estimates on 30-d intervals. A third-order or higher polynomial modeled the shape of variance curves over DIM with sufficient accuracy for the genetic and permanent environment part. Also, the genetic correlation structure was fitted with sufficient accuracy by a third-order polynomial, but, for the permanent environmental component, a fourth order was needed. Because equal orders are suggested in the literature, a fourth-order Legendre polynomial is recommended in this study. However, a rank of three for the genetic covariance matrix and of four for permanent environment allows a simpler covariance function with a reduced number of parameters based on the eigenvalues and eigenvectors.

Animals↗

PubMed2000

Genetic variation of susceptibility to Mycobacterium avium subsp. paratuberculosis infection in dairy cattle.

Paratuberculosis is an infectious disease that is not easily amenable to classical control methods such as treatment and vaccination. Experimental animal models suggest that there could be genetic factors responsible for susceptibility or resistance to infection with the causative agent, Mycobacterium avium subsp. paratuberculosis. The aim of this study was to estimate genetic variation in susceptibility to paratuberculosis in Dutch dairy cattle. Data collected during a vaccination trial, conducted from 1984 to 1994, was used. A total of 3020 cows, with complete pedigree records and infection status at slaughter, were available for analysis. A standard polygenic statistical probit model was used to estimate heritabilities. The estimated heritability of susceptibility to M. avium. subsp. paratuberculosis infection was 0.06 for the overall population. In the subpopulation of vaccinated animals the estimated heritability was 0.09. Other calculations based on the model used in this study argue against a prominent role for vertical transmission. Because the establishment of genetic variation is one of the first steps towards the exploration of the possible use of selection for genetic improvement, the present study provides evidence for the presence of genetic variation in the susceptibility of cattle to paratuberculosis. Because the economic impact of the disease is substantial, the development and application of genetic tools, along with other control methods, could be instrumental in the eradication of paratuberculosis.

Animals↗

PubMed1999

Detection of quantitative trait loci for backfat thickness and intramuscular fat content in pigs (Sus scrofa).

In an experimental cross between Meishan and Dutch Large White and Landrace lines, 619 F(2) animals and their parents were typed for molecular markers covering the entire porcine genome. Associations were studied between these markers and two fatness traits: intramuscular fat content and backfat thickness. Association analyses were performed using interval mapping by regression under two genetic models: (1) an outbred line-cross model where the founder lines were assumed to be fixed for different QTL alleles; and (2) a half-sib model where a unique allele substitution effect was fitted within each of the 19 half-sib families. Both approaches revealed for backfat thickness a highly significant QTL on chromosome 7 and suggestive evidence for a QTL at chromosome 2. Furthermore, suggestive QTL affecting backfat thickness were detected on chromosomes 1 and 6 under the line-cross model. For intramuscular fat content the line-cross approach showed suggestive evidence for QTL on chromosomes 2, 4, and 6, whereas the half-sib analysis showed suggestive linkage for chromosomes 4 and 7. The nature of the QTL effects and assumptions underlying both models could explain discrepancies between the findings under the two models. It is concluded that both approaches can complement each other in the analysis of data from outbred line crosses.

Adipose Tissue↗

PubMed1997

Bayesian statistical analyses for presence of single genes affecting meat quality traits in a crossed pig population.

Presence of single genes affecting meat quality traits was investigated in F2 individuals of a cross between Chinese Meishan and Western pig lines using phenotypic measurements on 11 traits. A Bayesian approach was used for inference about a mixed model of inheritance, postulating effects of polygenic background genes, action of a biallelic autosomal single gene and various nongenetic effects. Cooking loss, drip loss, two pH measurements, intramuscular fat, shearforce and back-fat thickness were traits found to be likely influenced by a single gene. In all cases, a recessive allele was found, which likely originates from the Meishan breed and is absent in the Western founder lines. By studying associations between genotypes assigned-to individuals based on phenotypic measurements for various traits, it was concluded that cooking loss, two pH measurements and possibly backfat thickness are influenced by one gene, and that a second gene influences intramuscular fat and possibly shearforce and drip loss. Statistical findings were supported by demonstrating marked differences in variances of families of fathers inferred as carriers and those inferred as noncarriers. It is concluded that further molecular genetic research effort to map single genes affecting these traits based on the same experimental data has a high probability of success.

Animals↗

PubMed1997

Segregation analyses for presence of major genes affecting growth, backfat, and litter size in Dutch Meishan crossbreds.

Presence of major genes was investigated for two growth traits, backfat thickness, and two litter size traits in the F1 and F2 population of a cross between Meishan and European "White" pig lines. Segregation analyses were performed in a Bayesian setting, estimating the contribution of background polygenes and the contribution of a possible major gene to the expression of the traits considered. In a first analysis, F1 and F2 crossbred data were evaluated; different error variances were fitted for F1 and F2 observations. In the first analysis, significant contributions of major-gene variance were found for the two growth traits, backfat thickness, and litter size at first parity. In a second analysis, F2 data were evaluated to determine whether biases were introduced in the joint analysis of F1 and F2 data. In the second analysis, no major genes were found for growth traits. Major genes affecting backfat and litter size at first parity were confirmed. The gene identified to affect backfat is a dominant gene; the homozygous recessive genotype has approximately 6 mm of additional backfat. The gene identified to affect litter size at first parity also is a dominant gene; the homozygous recessive genotype produces five to six fewer pigs per litter.

Animals↗

PubMed1993

A note on the estimation of the effective number of additive and dominant loci contributing to quantitative variation.

A method of estimating the number of loci contributing to quantitative variation has been proposed by S. Wright in 1921. The method makes use of the means of inbred lines and the variances of their F1, F2 and backcrosses. The method has been extended to crosses between outbreeding populations by R. Lande in 1981. Additive gene action is one of the major assumptions required for obtaining valid estimates. It is shown here that this assumption may be relaxed. One can estimate both a total number of effective loci and a number of dominant loci (the latter only when the parents are inbred) by comparing the variances of the F1, F2 and backcrosses. Numerical illustrations are given, based on crossbreeding data.

Animals↗

PubMed1993

Effect of divergent selection for immune responsiveness and of major histocompatibility complex on resistance to Marek's disease in chickens.

Lines of chickens selected for nine generations for high (H) or low (L) antibody response to SRBC, a randombred control (C) line, and an F1 cross between H and L lines were challenged for resistance to Marek's disease (MD). Hens only were challenged at day-old by contact with virulent MD Strain K. Birds were serologically typed for MHC erythrocyte antigens. Chicks from the L and H lines died earlier and later, respectively, than the C chicks, whereas time of death did not differ between F1 birds and the L chicks. Mortality in the L line (70.1%) was higher than in the C line (42.8%), but mortality in the H line (40.9%) was not lower than in the C line or the F1 cross (47.5%). Effects of MHC genotypes and haplotypes on mortality from MD were estimated within lines with a logistic regression model. Effect of MHC was moderate in the H line (P < .10) and highly significant in the C line (P < .005). Effects of MHC genotypes were similar in the H and C line but differed in the L and F1. Heritability of mortality from MD estimated with a threshold model including relationships between individuals was .40 when all lines were grouped together, whereas heritability estimated for each line separately was .45, .51, and .78 in the H, C, and L lines, respectively. Correlations between estimated breeding values for antibody response to SRBC and mortality from MD varied between lines and sexes. Correlations also were affected by whether or not the MHC effect was taken into account.

Animals↗