Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs.

BACKGROUND: Variants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with pigmentation phenotypes and risk of developing several types of skin cancer. OBJECTIVES: To evaluate OCA2/HERC2 locus variants for their impact on time to develop cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients (OTRs) who are at elevated risk of developing cSCC. METHODS: Participants were solid OTRs ascertained from two centres (n = 125 and 261) with an average of 13·1 years of follow-up post-transplant. DNA was available for genotyping for all participants, in addition to medical records and questionnaire data. The Ohio State University study had a case-control design with prospective follow-up, and the University of California San Francisco study was a national cross-sectional survey with retrospective chart review. RESULTS: OCA2 variants rs12913832 and rs916977 were significantly associated with time to first cSCC post-transplant. OTRs homozygous for the brown-eye alleles of rs916977 (GG) and rs12913832 (AA) had significant delays of time to first cSCC post-transplant compared with individuals homozygous for the blue-eye alleles (hazard ratio 0·34, P < 0·001 and hazard ratio 0·54, P = 0·012, respectively). Both variants were highly associated with eye colour in the combined studies (P < 0·001). CONCLUSIONS: This study is the first to show an association between OCA2/HERC2 variants and time to first cSCC post-transplant. This may impact dermatological screening recommendations for high-risk populations.

A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds.

In rabbit, the dilute locus is determined by a recessive mutated allele (d) that causes the dilution of both eumelanic and pheomelanic pigmentations. In mice, similar phenotypes are determined by mutations in the myosin VA, Rab27a and melanophilin (MLPH) genes. In this study, we investigated the rabbit MLPH gene and showed that a mutation in this gene appears responsible for the dilute coat colour in this species. Checkered Giant F1 families segregating for black and grey (diluted or blue) coat colour were first genotyped for a complex indel in intron 1 of the MLPH gene that was completely associated with the coat colour phenotype (θ = 0.00; LOD = 4.82). Then, we sequenced 6357 bp of the MLPH gene in 18 rabbits of different coat colours, including blue animals. A total of 165 polymorphisms were identified: 137 were in non-coding regions and 28 were in coding exons. One of them was a frameshift deletion in exon 5. Genotyping the half-sib families confirmed the complete cosegregation of this mutation with the blue coat colour. The mutation was analysed in 198 rabbits of 23 breeds. All Blue Vienna and all other blue/grey/ash rabbits in other breeds (Californian, Castor Rex, Checkered Giant, English Spot, Fairy Marburg and Fairy Pearly) were homozygous for this deletion. The identification of MLPH as the responsible gene for the dilute locus in rabbit provides a natural animal model for human Griscelli syndrome type 3 and a new mutant to study the role of this gene on pigmentation.

Genetic description of a divergent selection experiment in Angora rabbits with overlapping generations.

The chief aims of this paper were the following: (i) to describe the demography and genetic structure in two divergent selected lines for total fleece weight (TFW) of French Angora rabbits with overlapping generations; (ii) to describe the effects of inbreeding during an experiment of divergent selection. A study of longevity with the survival kit showed that there was no significant difference in the risk of death or culling between the low line (LL) and high line (HL). A significant effect of inbreeding (p < 0.05) was observed with a 30% higher risk factor in the highest class of inbreeding coefficient compared with the other classes. The means of generation interval were 562 and 601 days in LL and HL, respectively. The numbers of generations for LL and HL were 3.90 and 3.64, respectively. Generation intervals decreased significantly from 1995 to 2000 (p < 0.05). The number of daughters in HL was very variable. The number of animals per generation was higher in HL than in LL. Each buck left nearly three daughters to the next generation (2.52 in LL, 3.24 in HL). In both lines, the effective number of ancestor genomes still present in the genetic pool of the generation was around eight from the reference population of 1995 to that of 2001. Inbreeding in HL was always higher than in LL. The effect of inbreeding was also significant (p < 0.05) on TFW and live weight. The animals with the lowest inbreeding category produced a higher TFW (p < 0.05) than the others. The observed selection differentials were lower than that expected owing to the breeding animal management rules in order to control inbreeding increase.

Role of prolactin in the photoperiodic control of moulting in the mink (Mustela vison).

Beginning at the summer solstice adult female mink were maintained in long- or short-day photoperiods and treated with bromocriptine or prolactin. In control females kept under natural lighting conditions the moult coincided with the seasonal decrease in prolactin and resulted in the growth of a dense winter coat which was completed by the end of November. Long days, which slowed the decrease in plasma prolactin relative to animals in the natural photoperiod, induced a more or less complete moult followed by growth of a thin summer coat. On the contrary we observed an accelerated decrease in plasma prolactin concentrations followed by an early and brief moult in females kept under long days but treated with bromocriptine and in females under short days. The growth of a dense winter coat was completed by the end of September in all the females of the short-day group and in six of eleven females treated with bromocriptine. In the other five females, moult was followed by the growth of a summer coat. These results may suggest that the decline of prolactin after the summer solstice is responsible for the onset of the autumn moult, but the early, abbreviated moult and the growth of a winter coat observed in females kept under short days and treated with prolactin do not seem to support this hypothesis. However, the huge non-physiological levels of prolactin measured in the plasma of these females and the appearance of abnormal white under-hairs might suggest that the hormonal balance in this group was completely disturbed by the treatment. The physiological role of prolactin in the seasonal moulting cycle in mink is discussed.

Pineal denervation by cervical sympathetic ganglionectomy suppresses the role of photoperiod on pregnancy or pseudopregnancy, body weight and moulting periods in the mink (Mustela vison).

In mink, termination of the delayed implantation period, following reactivation of the corpora lutea, and onset of the spring moult are associated with a rise in prolactin secretion triggered by increasing daylength, while decreasing daylength induces the autumn moult. To establish whether suppression of the function of the pineal rendered the mink unresponsive to daylength changes, the superior cervical ganglion was removed bilaterally 2-4 weeks before mating. Intact and operated females were then left outdoors or were put under a lighting regime of either 15 h light:9 h darkness (15L:9D) or 8L:16D. In July, at the end of the spring moult, the 15L:9D lighting regime was changed to one of 8L:16D. Under artificial photoperiods ganglionectomy suppressed the stimulatory role of long days and the inhibitory role of short days on prolactin secretion, and consequently on progesterone secretion and spring moult. Neither was the autumn moult, induced early in intact females by the change to a short photoperiod, advanced in ganglionectomized females, showing that the latter were unresponsive to the artificial modification of the photoperiod. However, in animals kept outdoors, prolactin and progesterone secretion and spring moult were not changed by ganglionectomy. Increase in body weight and autumn moult were only slightly delayed by the operation suggesting that other environmental factors had replaced the synchronizing effect of the daylength changes. Alternatively the desynchronization between intact females responsive to photoperiodism and those rendered unresponsive may be too slow to be observed soon after ganglionectomy.

A direct agglutination test for leishmaniasis.

Antigen suspensions of enzyme-treated, formalin-fixed promastigotes of three species of Leishmania (L. donovani, L. tropica, and L. braziliensis) were evaluated by using the direct agglutination test with serum samples from healthy individuals and patients with confirmed cases of visceral and cutaneous leishmaniasis. High cross-reactivity was obtained with the three antigens in tests with leishmania sera. Sera from patients with kala-azar were 61% to 96% positive when tested with all three antigens. In tests with sera from patients with American cutaneous leishmaniasis, 81% were positive with L. donovania and L. braziliensis antigen, whereas only 54% to 55% were positive with the other two antigens. Normal sera were reactive at low dilutions of 1:16 or less with L. braziliensis antigens. Normal sera tested with L. tropica antigen reacted to a titer of 128.

Evaluation of the micro enzyme-linked immunosorbent assay for antibodies to Trypanosoma cruzi.

A micro enzyme-linked immunosorbent assay (ELISA) for antibodies to Trypanosoma cruzi was evaluated and the results obtained by ELISA were compared with those obtained by the complement fixation test (CF) and indirect fluorescent antibody test (IFA). Fifty sera collected from residents of the southeastern United States all had reciprocal ELISA titers less than or equal to 320. Similarly, serum samples from 17 patients with T. cruzi infection proven by xenodiagnosis had reciprocal ELISA titers of greater than or equal to 1,280. Specimens from 302 El Salvador Army recruits were tested by ELISA, IFA, and CF. Excellent correlation was observed between results obtained by the three serologic tests; 62.9% of the samples were negative by each of the three tests and 24.5% were positive by all. Overall, 29.5% of the sera were positive for antibodies to T. cruzi by ELISA, 29.5% by IFA, and 31.5% by CF. The data suggest that the micro ELISA is a promising serologic test for measuring antibodies to T. cruzi in individuals and in populations.

Autochthonous dermal leishmaniasis in Texas.

Over a 2-year period two cases of dermal leishmaniasis of special interest were recognized in Texas. The first occurred in 1972 in a 74-year-old woman who had residences in Dilworth and Gahzales, Gonzales County, and the other was in a 56-year-old man from Kenedy, Karnes County, in 1974. Both cases were biopsy- and culture-positive, and the second patient exhibited anti-Leishmania antibodies by indirect immunofluorescent antibody and direct agglutination tests. Epidemiologic investigation revealed no association between the two cases and suggested that both patients had acquired their infections locally in southern Texas. Moreover, serologic evidence of Leishmania infection was uncovered in a neighbor of the second case and in 3 dogs living nearby. Potential sylvatic reservoirs and arthropod vectors of the disease are resident in the area. Epidemiologic data suggest that dermal leishmaniasis is endemic in south-central Texas.

Effect of feed restriction on rabbit meat quality of the Rex du Poitou(®).

Two orylag(®) rabbit genotypes, Castor and Chinchilla, feed restricted from 8 to 18 weeks of age at 130 g/d or fed ad libitum, were compared for growth, feed efficiency, carcass traits, and meat sensory characteristics. The total body electrical conductivity (ToBEC) value was also measured to predict meat quality. The feeding level was more restrictive for Castor than for Chinchilla rabbits (74% and 90%, respectively). As expected, growth, feed efficiency, carcass yield and adiposity were altered in both genotypes with feed restriction. For restricted animals, tenderness, juiciness, flavour, flouriness, stickiness and fatness were not affected by the genotype. Feed restriction only significantly decreased flouriness in the Castor genotype. Correlations between meat characteristics and sensory traits were low, and the ToBEC value was not correlated with organoleptic quality.

Importance of birthcoat for lamb survival and growth in the Romane sheep breed extensively managed on rangelands.

The Romane sheep breed proved to be adapted to harsh conditions with high prolificacy and lamb survival in outdoor farming, even under bad climate conditions. This breed shows large variability in its fleece type at birth and it has been suggested that lamb survival could be related to birthcoat type. The aim of the present study was to: i) characterize the coat of the lamb at birth and quantify lamb survival in relation to the birthcoat type and its protective properties concerning heat loss in the Romane breed raised under permanent exposure outdoors from birth, and ii) estimate genetic parameters of birthcoat type in relation to lamb survival and live body weight. A total of 7,880 lambs from 104 sires and 1,664 dams were used in a 14-yr experiment. The pedigree file included 9,625 individuals over 15 generations. Birthcoat type, coat surface temperature, coat depth, lamb survival, and growth were measured from birth to weaning. Weather data (temperature, wind speed, relative humidity, and precipitation) were recorded daily during lambing time. Two types of coats were observed at birth: hairy coat (62.9% of lambs) with a long coat depth (average 23.3 mm) or woolly 1 (37.1% of lambs) with a short coat depth (average 8.3 mm). Birthcoat type was an important factor affecting lamb survival and growth from birth in the Romane breed. Total mortality rate was significantly less in hairy-bearing coat lambs than in short-woolly coat ones: 7.0% vs. 9.6%, 11.6 % vs. 14.8%, and 15.7 % vs. 20.1 % at 2, 10, and 50 d, respectively, and the relative risks of death increased by 37%, 67%, and 46 % at 2, 10, and 50 d of age, respectively, in short-woolly lambs. At birth, a significant lower coat surface temperature, indicating less heat loss, was observed in long-hairy coat lambs compared with others (21.1°C vs. 26.1°C). Heavier body weights and better growth performances up to the age of 50 d were observed in long-hairy-bearing coat lambs. Lamb survival was positively correlated to weather conditions at lambing time in short-woolly lambs, whereas no relation was observed in hairy-coat lambs. Heritability estimate of birthcoat type (hairy or woolly) is high (0.88). Genetic correlations between birthcoat type, lamb survival, and live body weight at birth were positive and moderate, suggesting that it would be beneficial to take birthcoat into account as an adaptive trait in any genetic strategies for sheep production in harsh conditions on rangelands.

Genetics of fibre production and fleece characteristics in small ruminants, Angora rabbit and South American camelids.

This paper reviews genetics of fibre production and fleece characteristics in small ruminants, Angora rabbit and South American camelids with a special distinction between single-coated (SC) and double-coated (DC) species. Considering the biology of fibre production, there are variations in coat composition and structure, fibre growth pattern and fibre structure and quality between these two main kinds of fibre-producing animals. In SC species, all fibres are nearly similar in dimensions and are produced from individual follicles that have a very long period, essentially permanent, of active growth without a synchronous phase of rest between follicles. In contrast, in DC species the fleece comprises a coarse outer coat and a fine inner coat with variations of coat composition and structure, and fibre growth pattern according to the season with a well-defined duration of fibre growth. Genetic basis of hair growth pattern, coat composition and fibre structure are different between species. In small ruminants, these coat characters are additive and because of several genes whereas in rabbit, several autosomal recessive genes determine fibre growth, coat composition and structure. In alpaca, the fleece type (Suri or Huacaya) is determined by a single dominant gene. This paper also reviews genetic parameters of fibre production traits in Angora goat, Angora rabbit and alpaca in which many aspects of the genetic basis of fibre production are analogous. There are many traits controlling both fibre quality and fibre quantity, and most of these traits tend to be moderately to strongly inherited so that a rapid genetic progress in any traits is possible and indeed has been achieved. However, there are differences in breeding programmes. In DC Angora rabbit, selection for one single trait, the easy measurable total fleece weight has general beneficial effects on fleece quality. However, because of antagonistic relations between qualitative and quantitative traits in SC species, achieving this goal requires a multi-trait selection index approach. Gene mapping studies have recently identified several putative quantitative trait loci and major genes affecting fibre and fleece characteristics in sheep, goat and rabbit are reviewed. The whole genome sequence of sheep and rabbit will be available in the near future and the use of high-density single nucleotide polymorphism chip will allow fine mapping and dissection of the genetic basis of many production traits including fibre production and fleece characteristics. The application of these techniques will thus contribute to improving the efficiency, profitability and sustainability of small ruminant and rabbit fibre production.

Merino sheep: a further look at quantitative trait loci for wool production.

A quantitative trait loci (QTL) analysis of wool traits from experimental half-sib data of Merino sheep is presented. A total of 617 animals distributed in 10 families were genotyped for 36 microsatellite markers on four ovine chromosomes OAR1, OAR3, OAR4 and OAR11. The markers covering OAR3 and OAR11 were densely spaced, at an average distance of 2.8 and 1.2 cM, respectively. Body weight and wool traits were measured at first and second shearing. Analyses were conducted under three hypotheses: (i) a single QTL controlling a single trait (for multimarker regression models); (ii) two linked QTLs controlling a single trait (using maximum likelihood techniques) and (iii) a single QTL controlling more than one trait (also using maximum likelihood techniques). One QTL was identified for several wool traits on OAR1 (average curvature of fibre at first and second shearing, and clean wool yield measured at second shearing) and on OAR11 (weight and staple strength at first shearing, and coefficient of variation of fibre diameter at second shearing). In addition, one QTL was detected on OAR4 affecting weight measured at second shearing. The results of the single trait method and the two-QTL hypotheses showed an additional QTL segregating on OAR11 (for greasy fleece weight at first shearing and clean wool yield trait at second shearing). Pleiotropic QTLs (controlling more than one trait) were found on OAR1 (clean wool yield, average curvature of fibre, clean and greasy fleece weightand staple length, all measured at second shearing).

Characteristics of Angora rabbit fiber using optical fiber diameter analyzer.

An experiment was conducted to describe the characteristics of Angora rabbit fiber using optical fiber diameter analyzer (OFDA). A total of 349 fleece samples were collected from 60 French Angora rabbits. Recorded measurements of OFDA were as follows: mean fiber diameter, CV of fiber diameter, comfort factor, spinning fineness, mean fiber curvature, SD of fiber curvature, mean opacity of fibers, percentage of medullated fibers, mean fiber diameter along the length, and SD of fiber diameter along the length. Comfort factor is the percentage of fibers less than or equal to 30 microns. The main effects included in the mixed model were fixed effects of group, harvest season, and age and a random effect of animal. Correlations among total fleece weight, compression, and OFDA measurements were calculated. Mean fiber diameter was lower than the fiber diameter along the length. Mean percentage of medullated fibers was very low and ranged from 0.1 to 7.3%. The mean comfort factor was 97.5% and ranged from 93.3 to 99.8%. The mean fiber curvature was 40.1 degrees/mm. The major changes in Angora fleece characteristics from 8 to 105 wk of age were an increase in fiber diameter, CV of fiber diameter, mean fiber diameter along the length and curvature, and a decrease in compression and comfort factor. The effect of harvest season was significant on some fiber characteristics. Mean fiber diameter and the mean fiber diameter along the length had a positive correlation with total fleece weight. The OFDA methodology is a method to evaluate fiber diameter, CV of fiber diameter, and bristle content through measuring of the comfort factor. However, OFDA is not adapted for measuring opacity or size of the medulla, or both, in Angora wool and needs a new definition or a special calibration. The spinning fineness should be redefined and adapted for Angora rabbits.

A first-generation microsatellite-based integrated genetic and cytogenetic map for the European rabbit (Oryctolagus cuniculus) and localization of angora and albino.

Although the European rabbit (Oryctolagus cuniculus) is used both in agronomics and in research, genomic resources for this species are still limited and no microsatellite-based genetic map has been reported. Our aim was to construct a rabbit genetic map with cytogenetically mapped microsatellites so as to build an integrated genetic and cytogenetic map. A reference population of 187 rabbits comprising eight three-generation families with 10-25 offspring per family was produced. One hundred and ninety-four of 305 previously identified microsatellites were included in this study. Of these, 158 were polymorphic with two to seven alleles. The map reported here comprises 111 markers, including 104 INRA microsatellites, five microsatellites from another source and two phenotypic markers (angora and albino). Ninety markers were integrated into 20 linkage groups. The remaining 21 microsatellites mapped to separate linkage groups, 19 with a precise cytogenetic position and two with only a chromosomal assignment. The genetic map spans 2766.6 cM and covers 20 rabbit chromosomes, excluding chromosomes 20, 21 and X. The density of this map is limited, but we used it to verify the location of angora and albino on chromosomes 15q and 1q, respectively, in agreement with previously published data. This first generation genetic/cytogenetic map will help gene identification and quantitative trait loci mapping projects in rabbit.