Assessment of inbreeding coefficients and inbreeding depression on complex traits from genomic and pedigree data in Nelore cattle.

BACKGROUND: Nelore cattle play a key role in tropical production systems due to their resilience to harsh conditions, such as heat stress and seasonally poor nutrition. Monitoring their genetic diversity is essential to manage the negative impacts of inbreeding. Traditionally, inbreeding and inbreeding depression are assessed by pedigree-based coefficients (F), but recently, genetic markers have been preferred for their precision in capturing the inbreeding level and identifying animals at risk of reduced productive and reproductive performance. Hence, we compared the inbreeding and inbreeding depression for productive and reproductive performance traits in Nelore cattle using different inbreeding coefficient estimation methods from pedigree information (FPed), the genomic relationship matrix (FGRM), runs of homozygosity (FROH) of different lengths (> 1 Mb (genome), between 1 and 2 Mb - FROH 1-2; 2-4 Mb FROH 2-4 or > 8 Mb FROH >8) and excess homozygosity (FSNP). RESULTS: The correlation between FPed and FROH was lower when the latter was based on shorter segments (r = 0.15 with FROH 1-2, r = 0.20 with FROH 2-4 and r = 0.28 with FROH 4-8). Meanwhile, the FPed had a moderate correlation with FSNP (r = 0.47) and high correlation with FROH >8 (r = 0.58) and FROH-genome (r = 0.60). The FROH-genome was highly correlated with inbreeding based on FROH>8 (r = 0.93) and FSNP (r = 0.88). The FGRM exhibited a high correlation with FROH-genome (r = 0.55) and FROH >8 (r = 0.51) and a lower correlation with other inbreeding estimators varying from 0.30 for FROH 2-4 to 0.37 for FROH 1-2. Increased levels of inbreeding had a negative impact on the productive and reproductive performance of Nelore cattle. The unfavorable inbreeding effect on productive and reproductive traits ranged from 0.12 to 0.51 for FPed, 0.19-0.59 for FGRM, 0.21-0.58 for FROH-genome, and 0.19-0.54 for FSNP per 1% of inbreeding scaled on the percentage of the mean. When scaling the linear regression coefficients on the standard deviation, the unfavorable inbreeding effect varied from 0.43 to 1.56% for FPed, 0.49-1.97% for FGRM, 0.34-2.2% for FROH-genome, and 0.50-1.62% for FSNP per 1% of inbreeding. The impact of the homozygous segments on reproductive and performance traits varied based on the chromosomes. This shows that specific homozygous chromosome segments can be signs of positive selection due to their beneficial effects on the traits. CONCLUSIONS: The low correlation observed between FPed and genomic-based inbreeding estimates suggests that the presence of animals with one unknown parent (sire or dam) in the pedigree does not account for ancient inbreeding. The ROH hotspots surround genes related to reproduction, growth, meat quality, and adaptation to environmental stress. Inbreeding depression has adverse effects on productive and reproductive traits in Nelore cattle, particularly on age at puberty in young bulls and heifer calving at 30 months, as well as on scrotal circumference and body weight when scaled on the standard deviation of the trait.

Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.

A homozygous p.Val120Leu (c.358G > C) SOD1 mutation led to slowly progressive amyotrophic lateral sclerosis in a Brazilian family.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease usually associated with severe weakness and death within 2-5 years. SOD1 mutations cause hereditary ALS in autosomal dominant and rarely in recessive pattern. We describe a new phenotype of slowly progressive fALS due to homozygous SOD1 mutations (c.358G > C, p.Val120Leu) in a Brazilian family. We reviewed the medical chart and interviewed the index patient and other relatives. A 41-year-old man developed weakness in his legs, leading to frequent falls, followed over the next few months with progressive arm fasciculations and muscle atrophy. The SOD1 enzymatic activity in erythrocytes was slightly decreased. A genetic test panel disclosed homozygous SOD1 mutations (c.358G > C, p.Val120Leu). His asymptomatic parents also carried one mutant allele and 2 brothers and a sister had died with ALS. We reported a new family with homozygous SOD1 mutation and slowly progressive ALS course. Further studies are necessary to confirm whether this mutation can also lead to disease in heterozygosis with incomplete penetrance.

Family sitosterolemia: report of two cases in Colombia. / Sitosterolemia familiar: reporte de dos casos en Colombia.

Sitosterolemia is an autosomal recessive and very rare disease. Its main characteristic is that there is a greater absorption and a decrease in the excretion of sterols, which leads to them being deposited in tissues. It is given by mutations in the ABCG5 or ABCG8 genes found on chromosome 2p21. In this clinical note, we describe the first two patients with familial sitosterolemia described in Colombia, brothers, one of them with xanthomas in extremities as the only symptom, and the other, completely asymptomatic. Genetic studies were performed as a diagnostic test in both patients, where a pathogenic homozygous variant could be identified in the ABCG8 gene in the first case (symptomatic), and a heterozygous variant in the ABCG8 gene in the second case (asymptomatic); the first patient has responded to treatment with ezetimibe. In conclusion, xanthomas should be studied in depth in pediatric age as they may be the only visible sign of such complex and hereditary diseases as familial sitosterolemia, which can be controlled and prevent cardiovascular complications of the disease.

ELMO2 biallelic pathogenic variants in a patient with gingival hypertrophy and cherubism phenotype: Case report and molecular review.

Ramon syndrome (OMIM #266270) was first described in a patient with cherubism, gingival fibromatosis, epilepsy, intellectual disability, hypertrichosis, and stunted growth. In 2018, Mehawej et al. described a patient with Ramon syndrome in whom a homozygous variant in ELMO2 was identified, suggesting that this gene may be the causative for this syndrome. ELMO2 biallelic pathogenic variants were also described in patients with a primary intraosseous vascular malformation (PIVM; OMIM #606893). These patients presented gingival bleeding and cherubism phenotype. Herein, a patient with gingival hypertrophy, neurodevelopmental delay, and cherubism phenotype with a novel homozygous predicted loss-of-function (LOF) variant in the ELMO2 gene and family recurrence was reported. A surgical approach to treat gingival bleeding and mandible vascular malformation was also described. Furthermore, this study includes a comprehensive literature review of molecular data regarding the ELMO2 gene. All the variants, except one described in the ELMO2, were predicted as LOF, including our patient's variant. There is an overlapping between PIVM, also caused by LOF biallelic variants in the ELMO2 gene, and Ramon syndrome, which can suggest that they are not different entities. However, due to a limited number of cases described with molecular evaluation, it is hard to establish a genotype-phenotype correlation. Our study supports that LOF pathogenic biallelic variants in the ELMO2 gene cause a phenotype that has cherubism and gingival hypertrophy as main characteristics.

Identification of runs of homozygosity (ROHs) in Curraleiro Pé-Duro and Pantaneiro cattle breeds.

This study aimed to identify and characterize runs of homozygosis (ROHs), genes involved in production characteristics and adaptation to tropical systems and to estimate the inbreeding coefficient of Curraleiro Pé-Duro (CPD) and Pantaneiro (PANT), two brazilian locally adapted cattle breeds. The results demonstrated that 79.25% and 54.29% of ROH segments were bigger than 8 Mb in CPD and PANT, respectively, indicating recent inbred matings in the studied population. Six homozygosis islands were identified simultaneously in both breeds, where 175 QTLs and 1072 genes previously described as associated with production traits are located. The inbreeding coefficient (FROH) estimated based on ROHs (FROH) showed that inbreeding is low (2 to 4%), which is different from expected for small populations such as locally adapted ones.

Assessment of runs of homozygosity, heterozygosity-rich regions and genomic inbreeding estimates in a subpopulation of Guzerá (Bos indicus) dual-purpose cattle.

For decades, inbreeding in cattle has been evaluated using pedigree information. Nowadays, inbreeding coefficients can be obtained using genomic information such as runs of homozygosity (ROH). The aims of this study were to quantify ROH and heterozygosity-rich regions (HRR) in a subpopulation of Guzerá dual-purpose cattle, to examine ROH and HRR islands, and to compare inbreeding coefficients obtained by ROH with alternative genomic inbreeding coefficients. A subpopulation of 1733 Guzerá animals genotyped for 50k SNPs was used to obtain the ROH and HRR segments. Inbreeding coefficients by ROH (FROH ), by genomic relationship matrix based on VanRaden's method 1 using reference allele frequency in the population (FGRM ), by genomic relationship matrix based on VanRaden's method 1 using allele frequency fixed in 0.5 (FGRM_0.5 ), and by the proportion of homozygous loci (FHOM ) were calculated. A total of 15,660 ROH were identified, and the chromosome with the highest number of ROH was BTA6. A total of 4843 HRRs were identified, and the chromosome with the highest number of HRRs was BTA23. No ROH and HRR islands were identified according to established criteria, but the regions closest to the definition of an island were examined from 64 to 67 Mb of BTA6, from 36 to 37 Mb of BTA2 and from 0.50 to 1.25 Mb of BTA23. The genes identified in ROH islands have previously been associated with dairy and beef traits, while genes identified on HRR islands have previously been associated with reproductive traits and disease resistance. FROH was equal to 0.095 ± 0.084, and its Spearman correlation with FGRM was low (0.44) and moderate-high with FHOM (0.79) and with FGRM_0.5 (0.80). The inbreeding coefficients determined by ROH were higher than other cattle breeds' and higher than pedigree-based inbreeding in the Guzerá breed obtained in previous studies. It is recommended that future studies investigate the effects of inbreeding determined by ROH on the traits under selection in the subpopulation studied.

Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Genotyping, sequencing and analysis of 140,000 adults from Mexico City.

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Reclassification of the HPGD p.Ala13Glu variant causing primary hypertrophic osteoarthropathy.

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.

Clinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome.

BACKGROUND: Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS. AIM: Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS). METHODS: Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene. RESULTS: Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6. CONCLUSIONS: Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.

A case of mitochondrial DNA depletion syndrome type 11 - expanding the genotype and phenotype.

Mitochondrial DNA depletion syndrome type 11 (MTDPS11) is caused by pathogenic variants in MGME1 gene. We report a woman, 40-year-old, who presented slow progressive drop eyelid at 11-year-old with, learning difficulty and frequent falls. Phisical examination revealed: mild scoliosis, elbow hyperextensibility, flat feet, chronic progressive external ophthalmoplegia with upper eyelid ptosis, diffuse hypotonia, and weakness of arm abduction and neck flexion. Investigation evidenced mild serum creatine kinase increase and glucose intolerance; second-degree atrioventricular block; mild mixed-type respiratory disorder and atrophy and granular appearance of the retinal pigment epithelium. Brain magnetic resonance showed cerebellar atrophy. Muscle biopsy was compatible with mitochondrial myopathy. Genetic panel revealed a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11 (c.862C>T; p.Gln288*). This case of MTDPS11 can contribute to the phenotypic characterization of this ultra-rare mitochondrial disorder, presenting milder respiratory and nutritional involvement than the previously reported cases, with possible additional features.

Genomic inbreeding estimation, runs of homozygosity, and heterozygosity-enriched regions uncover signals of selection in the Quarter Horse racing line.

With the advent of genomics, significant progress has been made in the genetic improvement of livestock species, particularly through increased accuracy in predicting breeding values for selecting superior animals and the possibility of performing a high-resolution genetic scan throughout the genome of an individual. The main objectives of this study were to estimate the individual genomic inbreeding coefficient based on runs of homozygosity (FROH ), to identify and characterize runs of homozygosity and heterozygosity (ROH and ROHet, respectively; length and distribution) throughout the genome, and to map selection signatures in relevant chromosomal regions in the Quarter Horse racing line. A total of 336 animals registered with the Brazilian Association of Quarter Horse Breeders (ABQM) were genotyped. One hundred and twelve animals were genotyped using the Equine SNP50 BeadChip (Illumina, USA), with 54,602 single nucleotide polymorphisms (SNPs; 54K). The remaining 224 samples were genotyped using the Equine SNP70 BeadChip (Illumina, USA) with 65,157 SNPs (65K). To ensure data quality, we excluded animals with a call rate below 0.9. We also excluded SNPs located on non-autosomal chromosomes, as well as those with a call rate below 0.9 or a p-value below 1 × 10-5 for Hardy-Weinberg equilibrium. The results indicate moderate to high genomic inbreeding, with 46,594 ROH and 16,101 ROHet detected. In total, 30 and 14 candidate genes overlap with ROH and ROHet regions, respectively. The ROH islands showed genes linked to crucial biological processes, such as cell differentiation (CTBP1, WNT5B, and TMEM120B), regulation of glucose metabolic process (MAEA and NKX1-1), heme transport (PGRMC2), and negative regulation of calcium ion import (VDAC1). In ROHet, the islands showed genes related to respiratory capacity (OR7D19, OR7D4G, OR7D4E, and OR7D4J) and muscle repair (EGFR and BCL9). These findings could aid in selecting animals with greater regenerative capacity and developing treatments for muscle disorders in the QH breed. This study serves as a foundation for future research on equine breeds. It can contribute to developing reproductive strategies in animal breeding programs to improve and preserve the Quarter Horse breed.

Unraveling the Molecular Basis of Mycosporine Biosynthesis in Fungi.

The Phaffia rhodozyma UCD 67-385 genome harbors a 7873 bp cluster containing DDGS, OMT, and ATPG, encoding 2-desmethy-4-deoxygadusol synthase, O-methyl transferase, and ATP-grasp ligase, respectively, of the mycosporine glutaminol (MG) biosynthesis pathway. Homozygous deletion mutants of the entire cluster, single-gene mutants, and the Δddgs-/-;Δomt-/- and Δomt-/-;Δatpg-/- double-gene mutants did not produce mycosporines. However, Δatpg-/- accumulated the intermediate 4-deoxygadusol. Heterologous expression of the DDGS and OMT or DDGS, OMT, and ATPG cDNAs in Saccharomyces cerevisiae led to 4-deoxygadusol or MG production, respectively. Genetic integration of the complete cluster into the genome of the non-mycosporine-producing CBS 6938 wild-type strain resulted in a transgenic strain (CBS 6938_MYC) that produced MG and mycosporine glutaminol glucoside. These results indicate the function of DDGS, OMT, and ATPG in the mycosporine biosynthesis pathway. The transcription factor gene mutants Δmig1-/-, Δcyc8-/-, and Δopi1-/- showed upregulation, Δrox1-/- and Δskn7-/- showed downregulation, and Δtup6-/- and Δyap6-/- showed no effect on mycosporinogenesis in glucose-containing medium. Finally, comparative analysis of the cluster sequences in several P. rhodozyma strains and the four newly described species of the genus showed the phylogenetic relationship of the P. rhodozyma strains and their differentiation from the other species of the genus Phaffia.

Runs of homozygosity and signatures of selection for number of oocytes and embryos in the Gir Indicine cattle.

Runs of homozygosity (ROH) and signatures of selection are the results of selection processes in livestock species that have been shown to affect several traits in cattle. The aim of the current work was to verify the profile of ROH and inbreeding depression in the number of total (TO) and viable oocytes (VO) and the number of embryos (EMBR) in Gir Indicine cattle. In addition, we aim to identify signatures of selection, genes, and enriched regions between Gir subpopulations sorted by breeding value for these traits. The genotype file contained 2093 animals and 420,718 SNP markers. Breeding values used to sort Gir animals were previously obtained. ROH and signature of selection analyses were performed using PLINK software, followed by ROH-based (FROH) and pedigree-based inbreeding (Fped) and a search for genes and their functions. An average of 50 ± 8.59 ROHs were found per animal. ROHs were separated into classes according to size, ranging from 1 to 2 Mb (ROH1-2Mb: 58.17%), representing ancient inbreeding, ROH2-4Mb (22.74%), ROH4-8Mb (11.34%), ROH8-16Mb (5.51%), and ROH>16Mb (2.24%). Combining our results, we conclude that the increase in general FROH and Fped significantly decreases TO and VO; however, in different chromosomes traits can increase or decrease with FROH. In the analysis for signatures of selection, we identified 15 genes from 47 significant genomic regions, indicating differences in populations with high and low breeding value for the three traits.

Analysis of the genomic landscape of inbreeding in two divergent groups of Spanish Florida goats.

The analysis of the genomic landscape of inbreeding using runs of homozygosity (ROH) patterns is becoming an interesting tool to partially understand phenotypic differences among individuals. In this study, we analysed genome-wide ROH patterns in two groups of Florida goats. We first determined the inbreeding levels of each individual by calculating ROH-based inbreeding coefficients (FROH ). Then, the individuals were divided into two groups based on FROH : high inbreeding (HI, FROH >0.1) and low inbreeding (LI, FROH <0.03). Finally, we performed an extensive in-depth analysis of ROH distribution in each group separately. We found a higher abundance of short ROH in LI, whereas long ROH was more frequent in HI. Furthermore, ROH abundance was not evenly distributed among chromosomes within groups, with some chromosomes showing larger numbers of ROH, like CHI6, CHI7 and CHI27. A different landscape was observed in recent inbreeding (ROH >8 Mb), with significant increases in CHI6, CHI11 and CHI28. Determination of genomic regions with significantly increased ROH (ROH islands-ROHi) showed 13 ROHi related to whole inbreeding and five ROHi associated with recent inbreeding analysis. Within these genomic regions, 123 and 101 genes were identified in HI and LI, respectively, including 10 and seven candidate genes previously related to production, fertility and heat resistance in goats and livestock species.

Pedigree reconstruction and population structure using SNP markers in Gir cattle.

Our objective was to establish a SNPs panel for pedigree reconstruction using microarrays of different densities and evaluate the genomic relationship coefficient of the inferred pedigree, in addition to analyzing the population structure based on genomic analyses in Gir cattle. For parentage analysis and genomic relationship, 16,205 genotyped Gir animals (14,458 females and 1747 males) and 1810 common markers to the four SNP microarrays were used. For population structure analyses, including linkage disequilibrium, effective population size, and runs of homozygosity (ROH), genotypes from 21,656 animals were imputed. Likelihood ratio (LR) approach was used to reconstruct the pedigree, deepening the pedigree and showing it is well established in terms of recent information. Coefficients for each relationship category of the inferred pedigree were adequate. Linkage disequilibrium showed rapid decay. We detected a decrease in the effective population size over the last 50 generations, with the average generation interval around 9.08 years. Higher ROH-based inbreeding coefficient in a class of short ROH segments, with moderate to high values, was also detected, suggesting bottlenecks in the Gir genome. Breeding strategies to minimize inbreeding and avoid massive use of few proven sires with high genetic value are suggested to maintain genetic variability in future generations. In addition, we recommend reducing the generation interval to maximize genetic progress and increase effective population size.

Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection.

In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aß. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.