Search

Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are pervasive, often lifelong disorders, lacking evidence-based interventions for core symptoms. With no established biological markers, diagnoses are defined by behavioral criteria. Thus, preclinical in vivo animal models of NDDs must be optimally utilized. For this reason, experts in the field of behavioral neuroscience convened a workshop with the goals of reviewing current behavioral studies, reports, and assessments in rodent models. Goals included: (a) identifying the maximal utility and limitations of behavior in animal models with construct validity; (b) providing recommendations for phenotyping animal models; and (c) guidelines on how in vivo models should be used and reported reliably and rigorously while acknowledging their limitations. We concluded by recommending minimal criteria for reporting in manuscripts going forward. The workshop elucidated a consensus of potential solutions to several problems, including revisiting claims made about animal model links to ASD (and related conditions). Specific conclusions included: mice (or other rodent or preclinical models) are models of the neurodevelopmental insult, not specifically any disorder (e.g., ASD); a model that perfectly recapitulates a disorder such as ASD is untenable; and greater attention needs be given to validation of behavioral testing methods, data analysis, and critical interpretation. ispartof: GENES BRAIN AND BEHAVIOR vol:21 issue:5 ispartof: location:England status: published

Aggressive (i.e. over-) feeding of broiler breeder females in the period preceding onset of lay results in higher mortality and subsequent deleterious effects on egg and chick production (the ‘over...

To fine map a quantitative trait locus (QTL) affecting milk production traits previously associated with microsatellite RM188, we implemented an interval mapping analysis by using microsatellite markers in a large Israeli Holstein half-sib sire family, and linkage disequilibrium (LD) mapping in a large set of US Holstein bulls. Interval mapping located the target QTL to the near vicinity of RM188. For the LD mapping, we identified 42 single nucleotide polymorphisms (SNP) in 15 genes in a 12-Mb region on bovine chromosome 4. A total of 24 tag SNP were genotyped in 882 bulls belonging to the University of California Davis archival collection of Holstein bull DNA samples with predicted transmitted ability phenotypes. Marker-to-marker LD analysis revealed 2 LD blocks, with intrablock r 2 values of 0.10 and 0.46, respectively; outside the blocks, r 2 values ranged from 0.002 to 0.23. A standard additive/dominance model using the generalized linear model procedure of SAS and the regression module of HelixTree software were used to test marker-trait associations. Single nucleotide polymorphism 9 on ARL4A, SNP10 on XR_027435.1, SNP12 on ETV1, SNP21 on SNX13, and SNP24 were significantly associated with milk production traits. We propose the interval encompassing ARL4A and SNX13 genes as a candidate region in bovine chromosome 4 for a concordant QTL related to milk protein traits in dairy cattle. Functional studies are needed to confirm this result.

Protein yield (PY) is currently the major economic product of the dairy herd. Genome-wide scans for quantitative trait loci (QTL) affecting milk yield (MY) and milk protein percentage (PP) suggest that of the loci affecting the 2 traits, about 1/4 exclusively affect MY, 1/4 exclusively affect PP, and half affect both traits. Because PY is the product of MY and PP, it is of interest to evaluate the expected effects on PY of marker-assisted selection (MAS) applied to these 3 classes of QTL. It is clear that selection for the appropriate allele at QTL exclusively affecting MY or PP will have a positive effect on PY. The question arises as to the effect of MAS directed at QTL affecting both MY and PP. Because the observed genetic correlation of about -0.5 between MY and PP must be generated by these loci, and because they comprise about half the total number of loci affecting the 2 traits, it can be inferred that the genetic correlation between MY and PP at loci affecting both traits is close to -1.0. This seems to imply that generally such loci would be neutral in their effects on PY. In the present study, biometrical expressions originally developed to describe the relationships of MY, fat percentage, and fat yield were adapted to describe the relationships of MY, PP, and PY. The resultant expressions were validated by showing that they correctly predicted the observed phenotypic standard deviation and heritability of PY, and the vastly different genetic correlations of PY with MY (very high positive) and of PY with PP (very low positive). Contrary to initial impressions, further biometrical analysis of the projected effects on PY of MAS at the loci affecting both traits, showed that even under the assumption that the genetic correlation between MY and PP at these loci is -1.0, selection for the allele favoring MY will have a strong positive effect on PY, whereas selection for the allele favoring PP will have an equal but opposite negative effect on PY. These diametrically opposed effects are due to the lower genetic coefficient variation of PP compared with MY. It is speculated that the reduced coefficient of variation of PP may be because of more stringent homeostatic buffering of milk composition compared with milk yield.

Although numerous quantitative trait loci (QTL) mapping studies involving milk protein percent (PP), milk yield (MY), and protein yield (PY) have been carried out, there has not been any systematic evaluation of the effects of individual QTL on these 3 interrelated traits. Consequently, the aim of the present study was to investigate the effects on MY and PY of QTL for PP previously mapped in various laboratories. The study, based on selective DNA pooling of milk samples, included 10 Israeli Holstein artificial insemination bulls, each the sire of 1,800 or more milk-recorded daughters. For each sire-trait combination across the 10 sires, milk samples of the highest and lowest daughters with respect to estimated breeding values for PP, PY, and MY were collected for pooling. A total of 134 dinucleotide microsatellites distributed over 25 bovine autosomes were used. An empirical standard error for marker-QTL linkage testing was calculated based on the variation among split samples within the same tail. Threshold comparison-wise error rate P-values were set to control proportion of false positives at P = 0.10 level for declaring significant effects at the marker-trait level. Estimates of the number of true null hypotheses for each trait were obtained from the histogram of marker comparison-wise error rate P-values. Based on these estimates, effective power of the experiment at the marker-trait level was estimated as 0.75, 0.41, and 0.73 for PP, PY, and MY. The proportion of heterozygosity at the QTL was estimated as 0.46, 0.39, and 0.40, respectively. After correcting for incomplete power and proportion of false positives, it was estimated that 38.7 and 37.5% of the markers affecting PP and MY, respectively, also affected PY. Of the markers affecting PY, 68.9 and 76.5%, respectively, also affected PP and MY. Apparently, none of the significant markers affected PY exclusively, and only 6.5 and 16.0%, respectively, affected PP or MY exclusively. Thus, almost all significant markers, and by inference almost all QTL, had effects on at least 2 of the 3 traits.

Quantitative trait loci (QTL) mapping projects have been implemented mainly in the Holstein dairy cattle breed for several traits. The aim of this study is to map QTL for milk yield (MY) and milk protein percent (PP) in the Brown Swiss cattle populations of Austria, Germany, and Italy, considered in this study as a single population. A selective DNA pooling approach using milk samples was applied to map QTL in 10 paternal half-sib daughter families with offspring spanning from 1,000 to 3,600 individuals per family. Three families were sampled in Germany, 3 in Italy, 1 in Austria and 3 jointly in Austria and Italy. The pools comprised the 200 highest and 200 lowest performing daughters, ranked by dam-corrected estimated breeding value for each sire-trait combination. For each tail, 2 independent pools, each of 100 randomly chosen daughters, were constructed. Sire marker allele frequencies were obtained by densitometry and shadow correction analyses of 172 genome-wide allocated autosomal markers. Particular emphasis was placed on Bos taurus chromosomes 3, 6, 14, and 20. Marker association for MY and PP with a 10% false discovery rate resulted in nominal P-values of 0.071 and 0.073 for MY and PP, respectively. Sire marker association tested at a 20% false discovery rate (within significant markers) yielded nominal P-values of 0.031 and 0.036 for MY and PP, respectively. There were a total of 36 significant markers for MY, 33 for PP, and 24 for both traits; 75 markers were not significant for any of the traits. Of the 43 QTL regions found in the present study, 10 affected PP only, 8 affected MY only, and 25 affected MY and PP. Remarkably, all 8 QTL regions that affected only MY in the Brown Swiss, also affected MY in research reported in 3 Web-based QTL maps used for comparison with the findings of this study (http://www.vetsci.usyd.edu.au/reprogen/QTL_Map/; http://www.animalgenome.org/QTLdb/cattle.html; http://bovineqtl.tamu.edu/). Similarly, all 10 QTL regions in the Brown Swiss that affected PP only, affected only PP in the databases. Thus, many QTL appear to be common to Brown Swiss and other breeds in the databases (mainly Holstein), and an appreciable fraction of QTL appears to affect MY or PP primarily or exclusively, with little or no effect on the other trait. Although QTL information available today in the Brown Swiss population can be utilized only in a within family marker-assisted selection approach, knowledge of QTL segregating in the whole population should boost gene identification and ultimately the implementation and efficiency of an individual genomic program.

Controlling the false discovery rate (FDR) has been proposed as an alternative to controlling the genomewise error rate (GWER) for detecting quantitative trait loci (QTL) in genome scans. The objective here was to implement FDR in the context of regression interval mapping for multiple traits. Data on five traits from an F2 swine breed cross were used. FDR was implemented using tests at every 1 cM (FDR1) and using tests with the highest test statistic for each marker interval (FDRm). For the latter, a method was developed to predict comparison-wise error rates. At low error rates, FDR1 behaved erratically; FDRm was more stable but gave similar significance thresholds and number of QTL detected. At the same error rate, methods to control FDR gave less stringent significance thresholds and more QTL detected than methods to control GWER. Although testing across traits had limited impact on FDR, single-trait testing was recommended because there is no theoretical reason to pool tests across traits for FDR. FDR based on FDRm was recommended for QTL detection in interval mapping because it provides significance tests that are meaningful, yet not overly stringent, such that a more complete picture of QTL is revealed.

The main force driving gene mapping in domestic animals, is the potential for using gene maps as a means of identifying and mapping the genetic loci responsible for genetic variation in traits of economic importance. The ultimate objective is utilizing this information for marker‐assisted selection (MAS) using DNA level polymorphisms. This overview considers: (1) The need for MAS, (2) The relationship of gene mapping to MAS, (3) Implementing MAS. Examples illustrating the potential contribution of MAS to animal genetic improvement are presented, including (I) Preselection of candidate bulls for progeny testing in dairy cattle improvement, (2) Introgression of trypanotolerance from N'Dama to other cattle breeds, and (3) Improvement of a successful layer cross.

Minisatellites, microsatellites, and short random oligonucleotides all uncover highly polymorphic DNA fingerprint patterns in Southern analysis of genomic DNA that has been digested with a restriction enzyme having a 4-bp specificity. The polymorphic nature of the fragments is attributed to tandem repeat number variation of embedded minisatellite sequences. This explains why DNA fingerprint fragments are uncovered by minisatellite probes, but does not explain how it is that they are also uncovered by microsatellite and random oligonucleotide probes. To clarify this phenomenon, we sequenced a large bovine genomic BamHI restriction fragment hybridizing to the Jeffreys 33.6 minisatellite probe and consisting of small and large Sau3A-resistant subfragments. The large Sau3A subfragment was found to have a complex architecture, consisting of two different minisatellites, flanked and separated by stretches of unique DNA. The three unique sequences were characterized by sequence simplicity, that is, a higher than chance occurrence of tandem or dispersed repetition of simple sequence motifs. This complex repetitive structure explains the absence of Sau3A restriction sites in the large Sau3A subfragment, yet provides this subfragment with the ability to hybridize to a variety of probe sequences. It is proposed that a large class of interspered tracts sharing this complex yet simplified sequence structure is found in the genome. Each such tract would have a broad ability to hybridize to a variety of probes, yet would exhibit a dearth of restriction sites. For each restriction enzyme having 4-bp specificity, a subclass of such tracts, completely lacking the corresponding restriction sites, will be present. On digestion with the given restriction enzyme, each such tract would form a large fragment. The largest fragments would be those that contained one or more long minisatellite tracts. Some of these large fragments would be highly polymorphic by virtue of the included minisatellite sequences; by virtue of their complex structure, all would be capable of hybridizing to a wide variety of probes, uncovering a DNA fingerprint pattern.

The association of cell chimerism with the freemartin condition, and of the absence of cell chimerism with normal female development, was confirmed by PCR amplification of a Y‐chromosome fragment in blood leukocytes and hair roots of cattle females co‐twin to males.

Results of a human observer performance study using a new ultrasound contrast‐detail (CD) phantom are reported. The new phantom allows estimates of the fundamental statistical uncertainties involved in CD analysis. Results of these experiments show that observers generally considered to be ‘‘trained’’ require experience at the specific task of low‐contrast target detection under signal known exactly (SKE) conditions, and that observers require an orientation period at the beginning of each observation session to obtain stable responses. The results obtained in this study can be used to estimate the number of independent images, observers, and repeat observation sessions required for a desired uncertainty in CD curves, and show that 10% fractional standard deviations are obtainable with modest observer effort.

Mastitis is an important and common dairy cattle disease affecting milk yield, quality, and consumer safety as well as cheese yields and quality. Animal welfare and residues of the antibiotics used to treat mastitis cause public concern. Considerable genetic variation may allow selection for increased resistance to mastitis. Because of high genetic correlation to milk somatic cell score (SCS), SCS can serve as a surrogate trait for mastitis resistance. The present study intended to identify quantitative trait loci (QTL) affecting SCS in Israeli and Italian Holstein dairy cattle (IsH and ItH, respectively), using selective DNA pooling with single and multiple marker mapping. Milk samples of 4,788 daughters of 6 IsH and 7 ItH sires were used to construct sire-family high- and low-tail pools, which were genotyped at 123 (IsH) and 133 (ItH) microsatellite markers. Shadow correction was used to obtain pool allele frequency estimates. Frequency difference between the tails and empirical standard error of D, SE(D), were used to obtain P-values. All markers significant by single marker mapping were also significant by multiple marker mapping, but not vice versa. Combining both populations, 22 QTL on 21 chromosomes were identified; all corresponded to previous reports in the literature. Confidence intervals were set by chi-squared drop method. Heterozygosity of QTL was estimated at 44.2%. Allele substitution effects ranged from 1,782 to 4,930 cells/mL in estimated breeding value somatic cell count units. Most (80%) of the observed variation in estimated breeding value somatic cell score could be explained by the QTL identified under the stringent criteria. The results found here can be used as a basis for further genome-wide association studies for the same trait.

A theoretical analysis of the potential benefits of marker-assisted selection (MAS) of candidate bulls prior to entry into a young sire progeny testing programme was carried out. It is assumed that quantitative trait loci (QTL) affecting milk production have been mapped with respect to known genetic markers, and MAS is based on evaluation of elite sires in order to identify marker alleles in coupling to favourable or unfavourable QTL alleles. Candidate bulls, descendants of the elite sire will then be selected, prior to conventional progeny testing, on the basis of the marker alleles derived from the elite-sire ancestor.The analysis considers recombination between marker and QTL, the difficulty of tracing specific marker alleles from sire to progeny, and the expectation that MAS, in practice, will be implemented in the grandsons, rather than in the sons of elite sires. It is shown that MAS of candidate bulls, based on the use of a single diallelic marker in linkage to a QTL will have only a negligible effect on the rate of genetic progress. Increases of 15 to 20% in the rate of genetic gain, however, can be obtained by the use of single polyallelic markers, and increases of 20 to 30% can be obtained by utilizing haplotypes of diallelic or polyallelic markers.

When heritability of the trait under investigation is low, replicated progenies can bring about a major reduction in the number of individuals that need to be scored for marker genotype in determining linkage between marker loci and quantitative trait loci (QTL). Savings are greatest when heritability of the trait is low, but are much reduced when heritability of the quantitative trait is moderate to high. Required numbers for recombinant inbred lines will be greater than those required for a simple F2 population when heritabilities are moderate to high and the proportion of recombination between marker locus and quantitative trait locus is substantial.

Length variation at the BTGL1 variable number of tandem repeat (VNTR) locus, which includes both minisatellite and microsatellite motifs, was examined in a wide sample of cattle. A total of 22 alleles were uncovered. The distribution of allele size variation implicated mechanisms involving both minisatellite and microsatellite sequences. This was confirmed by direct sequencing of two alleles. Differences between the two alleles involved repeat number variation of microsatellite motifs and a complex event involving the minisatellite motif, but point mutations were not observed.

Drosophila melanogaster sex peptide (SP) and Ductus ejaculatorius peptide (DUP99B) are male pheromones transferred in the seminal fluid to the female during copulation. Both reduce sexual receptivity and stimulate oviposition in females. The presence of high-affinity SP and DUP99B binding sites in the female were investigated by incubation of cryostat tissue sections with (125)I-iodinated peptides and subsequent autoradiography. We found that in adult females radiolabeled SP and DUP99B bind to peripheral nerves, the subesophageal ganglion, the cervical connective, to discrete parts of the thoracic ganglion, and to the genital tract. Weak and uniform labeling was detected in the neuropil of the brain and the thoracic ganglion. The labeling pattern in the nervous system suggests binding of the peptides to sensory afferents or glial cells. Scatchard analysis of the binding of (125)I-DUP99B to antennal nerves yielded a dissociation constant K(d) of 6.4 nM. Competition experiments with peptide fragments show that the peptides bind with their homologous C-terminal regions. Binding sites in the nervous system of females are established throughout sexual maturation. Prominent binding of the peptides to afferent nerves suggests modification of sensory input.

Previous studies using SSCP and PCR-RFLP methodologies uncovered nine polymorphic sites within the bGH gene, defining eight intragenic haplotypes falling into two main groups. In the present study we report the DNA sequence of these eight haplotypes. A total of 1494 bp were sequenced uncovering a total of 12 sequence variants. Haplotypes within groups differed among themselves at one or two sites, compared across groups, haplotypes of the two groups differed consistently at six sites, each of which was monomorphic within the respective groups. This comes to 4 differentiating sites per kb, suggesting that the two haplotype groups began to diverge about 400,000 years ago. This corresponds approximately to the estimated time of divergence of the Bos taurus and Bos indicus lineages, raising the possibility, supported by other evidence, that the two haplotype classes represent taurine and indicine haplotypes, respectively. Nucleotide sequence divergence of taurine and indicine genomes of this magnitude has far reaching implications with respect to QTL mapping and marker assisted selection in breeds derived from taurine x indicine crosses.

SSCP analysis of the bovine growth hormone (bGH) gene in Israel Holstein dairy cattle uncovered five intragenic haplotypes, denoted A to E. Of these, Haplotype E differed from the others at six fragments; one of which corresponded to the polymorphic MspI site in intron III, at which haplotype E carried the disabled MspI (-) allele. Haplotype E was observed in a single sire only, carrying haplotype A as the second bGH allele. In 523 daughters of this sire genotyped for the MspI polymorphism, heterozygous (+/-) as compared to homozygous (+/+) daughters, showed a significant increasing effect on protein percentage and kg protein per year; and a decreasing effect (P0.10) on milk somatic cell counts (MSSC). None of the daughters were homozygous (-/-), indicating that the frequency of this allele in the general population was essentially zero. Calculated skewness (g1) values for the two daughter groups differed significantly with (+/-) daughters showing negative skewness (in the direction of lower protein percentage), and (+/+) daughters positive skewness (in the direction of higher protein percentage). The direction of skewness in each group is indicative of the presence of a QTL having an increasing effect on milk protein percentage in coupling linkage with the MspI (-) allele in this sire, but at some distance from it. Maximum likelihood estimates of the proportion of recombination (r) between the putative QTL and bGH, and the allele substitution effect at the QTL (d), were r = 0.33, a = 0.07% protein, with standard errors 0.058 and 0.009% protein, respectively.

"Resolving power" is defined as the 95% confidence interval for quantitative trait locus (QTL) map location that would be obtained when scoring an infinite number of markers in a given constellation of a marker-QTL mapping experiment. Resolving power can serve as a close estimate of the confidence interval of QTL map location, as well as a guide to the lower efficient limit of marker spacing in an initial marker-QTL mapping experiment. In the present study, an extensive series of simulations was carried out to provide estimates of resolving power, for backcross (BC) and F2 designs, over a wide range of experimental sizes and of gene effects and dominance at the QTL. From the simulation results, the remarkably simple expressions, 3000/(mNd2) (where m = 1 for BC and m = 2 for F2; N = population size, and d = allele substitution effect) and 530/Nv (in terms of v, the proportion of variance explained), were obtained for estimating resolving power. These expressions can provide a convenient guide to planning marker spacing in BC and F2 marker-QTL linkage experiments and for placing confidence intervals about QTL map location obtained in such experiments.

Contrast-detail (CD) analysis was used to compare the low-contrast detection capabilities of expert observers using different array-type scanhead technologies. Five expert observers viewed five different contrast targets to obtain CD curves for each scanhead. Differences in CD curves are interpreted in terms of the image contrast, resolution, and noise. It was found that differences in low-contrast detectability were due to differences in beam properties. Clinical images obtained during patient examinations are used to show how some clinically relevant tasks are distributed in their contrast and size.

Results of a human observer performance study using a new ultrasound contrast-detail (CD) phantom are reported. The new phantom allows estimates of the fundamental statistical uncertainties involved in CD analysis. Results of these experiments show that observers generally considered to be "trained" require experience at the specific task of low-contrast target detection under signal known exactly (SKE) conditions, and that observers require an orientation period at the beginning of each observation session to obtain stable responses. The results obtained in this study can be used to estimate the number of independent images, observers, and repeat observation sessions required for a desired uncertainty in CD curves, and show that 10% fractional standard deviations are obtainable with modest observer effort.

The GH gene of Sparus aurata(saGH) contains variable number of tandem repeats (VNTR). The hyper-variable minisatellites in the first and third introns segregate in a Mendelian manner and exhibit numerous alleles. Analysis by PCR and sequencing of the two introns in several wild Sparidae species revealed comparable minisatellites with some variations. ‘Zoo blot’ with the first intron unit as a probe showed this sequence to be characteristic of several families from the Perciformes order. Unexpectedly, a similar minisatellite was found in the first intron of the GH gene in flounder, which belongs to a different order. Transfection of constructs containing a reporter gene and first intron of different length to four cell lines resulted in an inhibitory effect of the longer intron relative to the short intron. A (CA)n microsatellite (saGHpCA) is found in the GH promoter. A similar repeat at the same location is present in GH promoters of several other fish species. High variability (11 alleles) of the saGHpCA was found in a hatchery population. Full-sib family genotyping showed a Mendelian inheritance of these alleles. A significant association was found between allele distribution and body mass in large and average size fishes from a hatchery population. The intron minisatellites may serve as markers for hybrid population and parental assignment. Its presence in families and orders of the higher teleosts may help solving classification uncertainties. Their conservation and inhibitory effect suggest a biological role. The saGHpCA is correlated with growth and may be a good candidate for predicting growth performance.

This study explores the theoretical potential of "insertional mutagenesis" (i.e., mutagenesis as a result of integration of novel DNA sequences into the germ line), as a means of cloning quantitative trait loci (QTL). The approach presented is based on a direct search for mutagenic effects of a quantitative nature, and makes no assumptions as to the nature of the loci affecting quantitative trait value. Since there are a very large number of potential insertion sites in the genome but only a limited number of target sites that can affect any particular trait, large numbers of inserts will have to be generated and screened. The effects of allelic variants at any single QTL on phenotype value are expected to be small relative to sampling variation. Thus two of three stages of replicate testing will be required for each insert in order to bring overall Type I error down to negligible proportions and yet maintain good statistical power for inserts with true effects on the quantitative traits under consideration. The overall effort involved will depend on the spectrum of mutagenic effects produced by insertional mutagenesis. This spectrum is presently unknown, but using reasonable estimates, about 10,000 inserts would have to be tested, at reasonable replicate numbers (n ≧ 30) and Type I error (α=0.01) in the first testing stage, to provide a high likelihood of detecting at least one insert with a true effect on a given quantitative trait of interest. Total offspring numbers required per true quantitative mutagenic effect detected decrease strongly with increased number of traits scored and increased number of inserts per initial transformed parent. In fact, it would appear that successful implementation of experiments of this sort will require the introduction of multiple independent inserts in the original parent individuals, by means of repeated transformation, or use of transposable elements as inserts. When biologically feasible, selfing would appear to be the method of choice for insert replication, and in all cases the experiments must be carried out in inbred lines to reduce error variation due to genetic segregation, and avoid confounding mutational effects of the insert with effects due to linkage with nearby segregating QTL. The special qualifications of Arabidopsis thaliana for studies of this sort are emphasized, and problems raised by somaclonal variation are discussed.

SUMMARYRecords of 178 593 monoparous births between 1964 and 1970 in Israeli-Friesian dairy cattle were analysed for information on environmental and genetic factors affecting calving difficulties and perinatal mortality. The incidence of difficult calvings (DC) and peri-natal calf mortality (PM) were 6·9 and 9·1% in heifer calvings, and 1·6 and 4·1% in cow calvings. Calving characters were not related t o heifer age nor cow parity, but there was a seasonal trend in heifer calvings, with both DC and PM being high in winter and low in summer calvings.Heritability estimates for calf-genotype effects on PM were 0·042 in heifer calvings and 0·013 in cow calvings. Heritability estimates for dam-genotype effects on PM were 0·018 and 0·004 respectively. Heritability estimates for DC were similar t o those for PM. The genetic correlations between DC and PM in the same class of calvings ranged between 0·8 and 0·9, while the environmental correlations were considerably lower, about 0·3. The genetic correlations between the calf-genotype effects in heifer and cow calvings were about 0·5, indicating that different factors may affect heifer and cow calvings.It is proposed that sires already proven for milk yield be tested for their calf effects in heifer calvings, using contemporary comparisons within herds and seasons. Results will be available when the sires are 6 to 6½ yr old. Sires causing fewest calving difficulties would be nominated for heifer matings, so that most heifer inseminations would be by sires proven for both yield and calving characters. Some long-term progress might be obtained if sires with a high incidence of difficulties in their heifer mates were not used to produce young sires.

Since selection for growth-rate has been found to increase appetite and decrease maintenance requirements, it will lead to an increase in the excess of intake over maintenance. It is proposed that ...

By making use of pedigree information and information on marker-genotypes of the parent and F-1 individuals crossed to form an F-2 population, it is possible to carry out a linkage analysis between marker loci and loci affecting quantitative traits in a cross between segregating parent populations that are at fixation for alternative alleles at the QTL, but share the same alleles at the marker loci. For two-allele systems, depending on marker allele frequencies in the parent populations, 2-4 times as many F-2 offspring will have to be raised and scored for markers and quantitative traits in order to provide power equivalent to that obtained in a cross between fully inbred lines. Major savings in number of F-2 offspring raised can be achieved by scoring each parent pair for a large number of markers in each chromosomal region and scoring F-1 and F-2 offspring only for those markers for which the parents were homozygous for alternative alleles. For multiple allele systems, particularly when dealing with hypervariable loci, only 10%-20% additional F-2 offspring will have to be raised and scored to provide power equivalent to that obtained in a cross between inbred lines. When a resource population contains novel favorable alleles at quantitative trait loci that are not present (or rare) in a commercial population, analyses of this sort will enable the loci of interest to be identified, mapped and manipulated effectively in breeding programs.

1. Pen effects and sire x hatch interaction effects on growth rate to 8 weeks of age were estimated from family and progeny test data obtained from the application of two commercial breeding programmes for growth rate to broilers. 2. The following variance components were obtained: σ2(pen) = 255 g2, σ2(sire) = 1 260 g2, σ2(sire × hatch) = 1 997 g2,σ2(residual) = 19 708 g2. 3. It is concluded that the effectiveness of progeny testing for growth rate in broilers is severely restricted by sire x hatch interaction effects.

Methods are presented for determining linkage between a marker locus and a nearby locus affecting a quantitative trait (quantitative trait locus=QTL), based on changes in the marker allele frequencies in selection lines derived from the F-2 of a cross between inbred lines, or in the "high" and "low" phenotypic classes of an F-2 or BC population. The power of such trait-based (TB) analyses was evaluated and compared with that of methods for determining linkage based on the mean quantitative trait value of marker genotypes in F-2 or BC populations [marker-based (MB) analyses]. TB analyses can be utilized for marker-QTL linkage determination in situations where the MB analysis is not applicable, including analysis of polygenic resistance traits where only a part of the population survives exposure to the Stressor and analysis of marker-allele frequency changes in selection lines. TB analyses may be a useful alternative to MB analyses when interest is centered on a single quantitative trait only and costs of scoring for markers are high compared with costs of raising and obtaining quantitative trait information on F-2 or BC individuals. In this case, a TB analysis will enable equivalent power to be obtained with fewer individuals scored for the marker, but more individuals scored for the quantitative trait. MB analyses remain the method of choice when more than one quantitative trait is to be analyzed in a given population.

The use in dairy cattle improvement of loci associated with quantitative effects that might be found by genetic analysis is discussed. These methods can make a significant contribution only if they result in the identification of quantitative loci whose inheritance can be followed in a simple Mendelian manner. Another possibility, the identification of genetic components of production having a higher heritability than overall production, would make only a minor contribution to increased genetic progress. Selection of young males, according to the estimated breeding value associated by linkage with particular marker alleles in their sire, will not make a detectable contribution to genetic improvement.

The effects of days-open on milk yields in current lactations and in following lactations were estimated from 71 911 current and 68 693 following lactation records. Yields were expressed as 305-day, total and annual records, where annual record = 365 × (total yield/days between calvings).The data were grouped according to current days-open, corrected for initial yield differences and analysed separately for heifers and cows in Moshav (moderate-yielding) and Kibbutz (high-yielding) herds. Current 305-day records increased by 15 to 18 kg milk/day-open up to 90 days-open, and 2 to 3 kg/day-open thereafter. In contrast, the effects of increasing days-open on annual yields were generally small and negative, being positive only for heifers up to 90 days-open. Thus 305-day records heavily under-rated annual yields of fertile cows. For current lactations, 70 to 100 days-open for heifers and 30 to 50 days-open for cows resulted in the highest annual production. Yields in following lactations were positively associated with days-open in the previous lactation. The effect was highest in high-yielding herds, suggesting that high-yielding cows respond positively to some rest between calvings.Combining the effects of days-open on current and following lactation yields and on the calf crop: in high-yielding herds heifers had the highest productivity when mated not earlier than 70 days post partum, while in moderately-yielding herds days-open did not affect productivity. Cows in high-yielding herds achieved highest productivity at 41 to 90 days-open, while cows in moderately-yielding herds were most productive when mated as early as possible.A comparison of the economic value of sire fertility and sire transmitting ability for milk production showed that fertility may often be over-rated.

Data were collected during 1961–2 on the live-weight, age and warm carcass weights of 83 lots of Israel-Friesian bull calves, 525 animals in all, the offspring of 26 sires. For varying numbers of these animals weight of various non-saleable fat components, including ruminal fat, kidney fat, inguinal fat and scapular fat were also obtained. Ruminal fat alone and ruminal fat plus kidney fat were found to be highly correlated with total non-saleable fat (r = 0·84 and 0·94, respectively). Heritability of dressing percentage was 0·20, of live-weight rate-of-gain 0·92, and of carcass rate-ofgain 0·49. The genetic correlation between live-weight and carcass weight was 0·7. Between-lot correlations indicated that increased rate-of-gain achieved through management will be accompanied by decreased dressing percentage and increased non-saleable fat content.

NUMEROUS studies have shown that the dominant gene (P) for polledness found in the Saanen breed of dairy goats is associated with a recessive hermaphroditic effect, characterized by incomplete penetrance. The penetrance of the hermaphroditic effect increases with increasing litter size'''-. The Saanen breed is also characterized by an abnormal sex ratio at birth, the female class being deficient•'. The sex ratio becomes more normal, but not completely so, when hermaphrodites are counted with the females. This, and the fact that breeding tests show most, if not all, polled females to be heterozygous, seem to indicate that hermaphrodites are genetically female. Brandsch examined the relation between the proportion of polled offspring among the progeny of individual polled sires, and the sex ratio found within these progeny groups. He found that as the percentage of polled offspring increased, the sex ratio became more aberrant, even when hermaphrodites were included with the females. Laor et. al. noted a significant deficiency of females among the offspring of matings between homozygous polled males and polled females, again even when hermaphrodites were counted as females. These observations suggested that the abnormal sex ratio in the Saanen breed might also be a recessive effect of the genetic factor for polledness. This study was carried out to investigate this possibility.

Additional observations on a Robertsonian translocation segregating in the Saanen goat are reported. All of the animals born in this series of matings had balanced karyotypes, and all were phenotypically normal. Six translocation homozygotes were born, five females and one male. Three of the female homozygotes gave birth to phenotypically normal offspring. In five of seven twin pairs, both members of the pair had identical karyotypes with respect to the translocation chromosome and the sex chromosomes. The translocation chromosome was found more frequently among offspring born as singles, whereas the normal chromosome complement appeared more frequently among offspring born in multiple births. The data did not support the notion that this translocation possessed meiotic drive, either independently or in conjunction with the X or Y chromosome.

The genetic progress in live-weight-for-age (LFA), milk production, and in overall economic value expected as a result of performance and progeny testing of young bulls with respect to milk production and LFA was computed. It was shown that performance testing can contribute considerably to overall progress in economic value, while under certain circumstances progeny testing for LFA can also contribute to genetic progress in overall economic value, but to a lesser degree than performance testing. The relative economic value of LFA and milk production was derived and found to be relatively stable under differing economic conditions.

Synopsis Data from a reciprocal recurrent selection (RRS) programme involving a White Leghorn and a New Hampshire flock were analysed to determine whether there were genetic differences in the purebred population that came to expression primarily in the crossbred progeny. The RRS programme had been in use for four years. The White Leghorn flock had previously been the subject of long‐continued and intensive family selection. The New Hampshire flock was less highly selected. Egg number, egg weight and body weight were the primary traits under selection. Each year the programme involved about 10 sires and 80 females of each breed, and about 400 offspring of each type of cross. The overall economic value of the crossbreds consistently exceeded the mid‐parent mean, the difference increased steadily during the RRS programme. Heritabilities of the various traits were higher when calculated on the basis of crossbred offspring than when calculated on the basis of purebred offspring. For egg production in the Whit...

A family of Saanen goats is described in which centric fusion of two acrocentric chromosomes, giving rise to a submetacentric chromosome, has apparently occurred. The complement appeared to be genetically balanced, no phenotypic abnormalities being detected in six carriers or their offspring.

Genetic studies have shown that the dominant gene for polledness found in the Saanen breed will, when homozygous, lead to pseudohermaphrodism, testicular hypoplasia or epididymal sperm granuloma and to an abnormal sex ratio (excess of males). An analysis of chromosomal constitution and nuclear appendages in peripheral leucocytes and tissue cultures of 17 pseudohermaphrodites, 10 males with epididymal sperm granuloma and 3 males with testicular hypoplasia was carried out. Sex chromatin could not be unequivocally distinguished in buccal or urinary bladder smears owing to the presence of other large chromatin masses. In no case was any trace of ovarian tissue found. One pseudohermaphrodite was a blood chimaera (XX/XY). This animal, a typical freemartin, was indistinguishable in anatomy or histology from the other pseudohermaphrodites. The chromosomal constitution and nuclear appendages of the remaining 16 pseudohermaphrodites and of the males with testicular hypoplasia were those of a genetic female. It is concluded that the pseudohermaphroditic effect of the polled gene is limited to genetic females and that males with testicular hypoplasia are actually genetic females showing an extreme pseudohermaphroditic effect. The abnormal sex ratio characteristic of the Saanen breed is thus shown to be a trivial consequence of classifying extreme pseudohermaphrodites as males. The chromosomal constitution and nuclear appendages of the males with epididymal sperm granuloma were those of a normal male. Hence the genetic factor for polledness, when homozygous in genetic males, can lead to the development of epididymal sperm granuloma.