Transgenerational effects of the maternal gestational environment on the post-natal performance of beef cattle: A reaction norm approach.

In tropical beef cattle production systems, animals are commonly raised on pastures, exposing them to potential stressors. The end of gestation typically overlaps with a dry period characterized by limited food availability. Late gestation is pivotal for fetal development, making it an ideal scenario for inter- and transgenerational effects of the maternal gestational environment. Intergenerational effects occur due to exposure during gestation, impacting the development of the embryo and its future germline. Transgenerational effects, however, extend beyond direct exposure to the subsequent generations. The objective of the present study was to verify these effects on the post-natal performance of zebu beef cattle. We extended the use of a reaction norm model to identify genetic variation in the animals' responses to transgenerational effects. The inter- and transgenerational effects were predominantly positive (-0.09% to 19.74%) for growth and reproductive traits, indicating improved animal performance on the phenotypic scale in more favourable maternal gestational environments. Additionally, these effects were more pronounced in the reproductive performance of females. On average, the ratio of direct additive genetic variances of the slope and intercept of the reaction norm ranged from 1.23% to 3.60% for direct and from 10.17% to 11.42% for maternal effects. Despite its relatively modest magnitude, this variation proved sufficient to prompt modifications in parameter estimates. The average percentage variation of direct heritability estimates ranged from 19.3% for scrotal circumference to 33.2% for yearling weight across the environmental descriptors evaluated. Genetic correlations between distant environments for the studied traits were generally high for direct effects and far from unity for maternal effects. Changes in EBV rankings of sires across different gestational environments were also observed. Due to the multifaceted nature of inter- and transgenerational effects of the maternal gestational environment on various traits of beef cattle raised under tropical pasture conditions, they should not be overlooked by producers and breeders. There were differences in the specific response of beef cattle to variations in the quality of the maternal gestational environment, which can be partially explained by transgenerational epigenetic inheritance. Adopting a reaction norm model to capture a portion of the additive variance induced by inter- or transgenerational effects could be an alternative for future research and animal genetic evaluations.

Mapping genomic regions for reproductive traits in beef cattle: Inclusion of the X chromosome.

Although the second largest chromosome of the genome, the X chromosome is usually excluded from genome-wide association studies (GWAS). Considering the presence and importance of genes on this chromosome that are involved in reproduction, the aim of this study was to evaluate the effect of its inclusion in GWAS on reproductive traits (scrotal circumference [SC], early pregnancy [P16] and age at first calving [AFC]) in a Nelore herd. Genotype data from 3,263 animals with the above-mentioned phenotypes were used. The results showed an increase in the variances explained by the autosomal markers for all traits when the X chromosome was not included. For SC, there was an increase of more than 10% for the windows on chromosomes 2 and 6. For P16, the effect was increased by almost 20% for windows on chromosome 5. The same pattern was found for AFC, with an increase of more than 10% for the most important windows. The results indicate that the noninclusion of the X chromosome can overestimate the effects of autosomes on SC, P16 and AFC not only because of the additive effect of the X chromosome itself but also because of its epistatic effect on autosomal genes.

A note on transgenerational epigenetics affecting egg quality traits in meat-type quail.

1. The aim of the following experiment was to estimate transgenerational epigenetic variance for egg quality traits using genealogical and phenotypic information in meat-type quail. Measured traits included egg length (EL) and width (EWD), albumen weight (AW), shell weight (SW), yolk weight (YW) and egg weight (EW). 2. A total of 391 birds were evaluated for egg quality by collecting a sample of one egg per bird, during three consecutive days, starting on the 14th d of production. Analyses were performed using mixed models including the random epigenetic effect. Variance components were estimated by the restricted maximum likelihood method. A grid-search for values for the auto-recursive parameter (λ) was used in the variance components estimation. This parameter is directly related to the reset (v) and epigenetic transmissibility (1 - v) coefficients. 3. The epigenetic effect was not significant for any of the egg quality traits evaluated. Direct heritability estimates for egg quality traits ranged in magnitude from 0.06 to 0.33, whereby the higher estimates were found for AW and SW. Epigenetic heritability estimates were low and close to zero (ranging from 0.00 to 0.07) for all evaluated traits. 4. The current breeding strategies accounting for additive genetic effect seem to be suitable for egg quality traits in meat-type quail.

Transgenerational epigenetic variance for body weight in meat quails.

We aimed to estimate transgenerational epigenetic variance for body weight using genealogical and phenotypic information in meat quails. Animals were individually weighted from 1 week after hatching, with weight records at 7, 14, 21, 28, 35 and 42 days of age (BW7, BW14, BW21, BW28, BW35 and BW42, respectively). Single-trait genetic analyses were performed using mixed models with random epigenetic effects. Variance components were estimated by the restricted maximum likelihood method. A grid search for values of autorecursive parameter (λ) ranging from 0 to 0.5 was used in the variance component estimation. This parameter is directly related to the reset coefficient (ν) and the epigenetic coefficient of transmissibility (1-ν). The epigenetic effect was only significant for BW7. Direct heritability estimates for body weight ranged in magnitude (from 0.15 to 0.26), with the highest estimate for BW7. Epigenetic heritability was 0.10 for BW7, and close to zero for the other body weights. The inclusion of the epigenetic effect in the model helped to explain the residual and non-Mendelian variability of initial body weight in meat quails.

Identification of SNP c. -22G>A in the melanophilin gene from a dog with color dilution alopecia: case report / Identificação do SNP c. -22G>A no gene da melanophilina em um cão com alopecia por diluição da cor: relato de caso

Mutant color alopecia is an ectodermical defection of color dilution, characterized by partial alopecia, dry, shine-less hair, and peeling and papule. Melanization damages also occur on the cortical structure of the affected hair. The animals affected have big melanin grains with irregular shape on the basal keratinocytes, also on the hair matrix cells and rod. Therefore, there is not a specific treatment that makes any difference on the syndrome evolution. Although in some animals, it is possible to use weekly showers with benzyl peroxide to reduce seborrhea formation and secondary infections. There is evidence that the condition in dogs is caused by a single nucleotide polymorphism in the gene encoding the melanophilin protein. In the present study the identification of the SNP c.-22G>A in the melanophilin gene of a Dachshund breed dog with clinical and histopathologic evidence of color dilution alopecia is reported.(AU)

Alopecia por diluição da cor é um defeito ectodérmico caracterizado por alopecia parcial, pelagem seca e sem brilho, escamação e pápulas em áreas com defeitos na melanização e na estrutura cortical dos pelos. Os animais acometidos têm grânulos de melanina grandes e com formato irregular nos ceratinócitos basais, nas células da matriz dos pelos e nas hastes pilosas. Não existe tratamento específico que altere a evolução da síndrome, mas, em alguns animais, podem ser benéficos banhos semanais com xampu de peróxido de benzoíla, para reduzir a formação de seborreia e infecções secundárias. Há evidências de que a condição em cães é causada por uma mutação de ponto no gene que codifica a proteína melanophilina. No presente estudo, é relatada a identificação da mutação SNP c.-22G>A no gene da melanophilina em um cão da raça Dachshund com evidências clínicas e histopatológicas de alopecia por diluição da cor.(AU)

Identification of SNP c. -22G>A in the melanophilin gene from a dog with color dilution alopecia: case report / Identificação do SNP c. -22G>A no gene da melanophilina em um cão com alopecia por diluição da cor: relato de caso

Mutant color alopecia is an ectodermical defection of color dilution, characterized by partial alopecia, dry, shine-less hair, and peeling and papule. Melanization damages also occur on the cortical structure of the affected hair. The animals affected have big melanin grains with irregular shape on the basal keratinocytes, also on the hair matrix cells and rod. Therefore, there is not a specific treatment that makes any difference on the syndrome evolution. Although in some animals, it is possible to use weekly showers with benzyl peroxide to reduce seborrhea formation and secondary infections. There is evidence that the condition in dogs is caused by a single nucleotide polymorphism in the gene encoding the melanophilin protein. In the present study the identification of the SNP c.-22G>A in the melanophilin gene of a Dachshund breed dog with clinical and histopathologic evidence of color dilution alopecia is reported.(AU)

Alopecia por diluição da cor é um defeito ectodérmico caracterizado por alopecia parcial, pelagem seca e sem brilho, escamação e pápulas em áreas com defeitos na melanização e na estrutura cortical dos pelos. Os animais acometidos têm grânulos de melanina grandes e com formato irregular nos ceratinócitos basais, nas células da matriz dos pelos e nas hastes pilosas. Não existe tratamento específico que altere a evolução da síndrome, mas, em alguns animais, podem ser benéficos banhos semanais com xampu de peróxido de benzoíla, para reduzir a formação de seborreia e infecções secundárias. Há evidências de que a condição em cães é causada por uma mutação de ponto no gene que codifica a proteína melanophilina. No presente estudo, é relatada a identificação da mutação SNP c.-22G>A no gene da melanophilina em um cão da raça Dachshund com evidências clínicas e histopatológicas de alopecia por diluição da cor.(AU)

Identification of SNP c.-22G>A in the melanophilin gene from a dog with color dilution alopecia: case report

ABSTRACT Mutant color alopecia is an ectodermical defection of color dilution, characterized by partial alopecia, dry, shine-less hair, and peeling and papule. Melanization damages also occur on the cortical structure of the affected hair. The animals affected have big melanin grains with irregular shape on the basal keratinocytes, also on the hair matrix cells and rod. Therefore, there is not a specific treatment that makes any difference on the syndrome evolution. Although in some animals, it is possible to use weekly showers with benzyl peroxide to reduce seborrhea formation and secondary infections. There is evidence that the condition in dogs is caused by a single nucleotide polymorphism in the gene encoding the melanophilin protein. In the present study the identification of the SNP c.-22G>A in the melanophilin gene of a Dachshund breed dog with clinical and histopathologic evidence of color dilution alopecia is reported.

RESUMO Alopecia por diluição da cor é um defeito ectodérmico caracterizado por alopecia parcial, pelagem seca e sem brilho, escamação e pápulas em áreas com defeitos na melanização e na estrutura cortical dos pelos. Os animais acometidos têm grânulos de melanina grandes e com formato irregular nos ceratinócitos basais, nas células da matriz dos pelos e nas hastes pilosas. Não existe tratamento específico que altere a evolução da síndrome, mas, em alguns animais, podem ser benéficos banhos semanais com xampu de peróxido de benzoíla, para reduzir a formação de seborreia e infecções secundárias. Há evidências de que a condição em cães é causada por uma mutação de ponto no gene que codifica a proteína melanophilina. No presente estudo, é relatada a identificação da mutação SNP c.-22G>A no gene da melanophilina em um cão da raça Dachshund com evidências clínicas e histopatológicas de alopecia por diluição da cor.

Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings.

OBJECTIVE: Monogenic congenital cataract is one of the most genetically heterogeneous ocular conditions with almost 30 different genes involved in its etiology. In adult patients, genotype-phenotype correlations are troubled by eye surgery during infancy and/or long-term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency as the cause of autosomal recessive congenital cataract in a family from Costa Rica. METHODS: Four affected siblings were included in the study. All of them underwent eye surgery during the first decade but medical records were not available. Congenital cataract was diagnosed by report. Molecular analysis included genome wide homozygosity mapping using a 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene. RESULTS: Genome wide homozygosity mapping revealed a 6Mb region of homozygosity shared by two affected siblings at 17q25. The GALK1 gene was included in this interval and direct sequencing of this gene revealed a homozygous c.1144C>T mutation (p.Q382) in all four affected subjects. CONCLUSIONS: This work demonstrates the utility of homozygosity mapping in the retrospective diagnosis of a family with congenital cataracts in which ocular surgery at early age, the lack of medical records, and the presence of long term eye complications, impeded a clear clinical diagnosis during the initial phases of evaluation.

Polymorphism analysis and new JAG1 gene mutations of Alagille syndrome in Mexican population.

Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20-89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population.

Identificación de genes causales y de susceptibilidad para enfermedades de herencia mendeliana y compleja / Identification of susceptibility and causing genes for mendelian and complex diseases

Los factores genéticos participan en la etiología de la mayoría de las enfermedades comunes en la población. Las enfermedades en las que participan factores genéticos pueden ser clasificadas en varias categorías y de acuerdo con las características que presenten, se pueden utilizar distintas estrategias metodológicas para identificar los genes participantes. En la mayoría de las enfermedades con un patrón de herencia mendeliana, se han podido identificar las mutaciones causales de la enfermedad. En las enfermedades complejas, esta búsqueda ha sido menos exitosa a pesar de ser las más frecuentes en la población. Encontrar genes de susceptibilidad es importante no solo para entender el mecanismo de acción de la enfermedad, sino que podría contribuir en el desarrollo de medicamentos más eficaces para el tratamiento, conocer los factores ambientales y desarrollar intervenciones preventivas y, en algunos casos, la aplicación de terapia génica.

Genetic factors are involved in the etiology of most common diseases and traits present in populations. Different methodological approaches can be utilized to determine genes involvedaccording to their genetic features in diseases. In the majority of conditions that follow a simple Mendelian pattern culprit genetic mutations have been identified. Conversely complex traits that are most common in the population are also the most difficult to identify. Finding these genes is crutial no just to clarify the pathophysiology of these common diseases but also to identifyenvironmental factors involved and to improve their treatment, including in some specific cases gene therapy.