143 GENOMIC ASSESSMENT ASSOCIATIONS OF THE PATERNAL EFFECT FOR DAUGHTER FERTILITY TRAITS IN HOLSTEIN CATTLE

2016 ◽  
Vol 28 (2) ◽  
pp. 201
Author(s):  
A. A. Sermyagin ◽  
E. A. Gladyr ◽  
O. S. Romanenkova ◽  
A. N. Ermilov ◽  
G. Brem ◽  
...  
Keyword(s):  
Genomic Variation ◽  
Gestation Length ◽  
Holstein Cattle ◽  
Ministry Of Education ◽  
Loss Of Function ◽  
Scientific Organizations ◽  
A Genome ◽  
Recent Developments ◽  
Estimated Breeding Values ◽  
Fertility Traits

A worldwide decline of fertility in Holsteins requires the reliable evaluation of fertility traits. Because of the low heritability of most fertility traits, the reliabilities of bull estimated breeding values (EBV) for these traits are usually low. Recent developments in molecular genetics have opened the possibilities of identifying and using genomic variation that can significantly boost the reliabilities of EBV. Furthermore, some of the fertility problems can be caused by embryonic lethality due to LoF (loss of function) mutations. The objective of our study was to identify loci associated with fertility-related traits in Russian Holstein cattle and to evaluate the distribution of several LoF mutations associated with fertility in the Russian Holstein bull population. A genome-wide scan was performed on 195 progeny-tested and 61 young bulls genotyped with the 50K Illumina BeadChip (Illumina Inc., San Diego, CA, USA). The analysis was carried out using EBV for gestation length (GL), calving interval (CI), conception rate (CR), and days to the first insemination (DI) calculated by best linear unbiased prediction (BLUP) SM methodology. To increase the prediction reliability of associations, genomic EBV (GEBV) for young bulls were obtained using an genomic BLUP (GBLUP) approach. Furthermore, the bulls were genotyped by PCR or PCR-RFLP for LoF mutations in FANCI, APAF1, and GART genes, which are associated with brachyspina (BY) and fertility haplotypes HH1 and HH3. The single nucleotide polymorphism (SNP) quality check and association analysis was performed using Plink (1.09) software. In total, 43 101 SNP passed quality control. The average number of daughters per sire was ~215. Bonferroni correction test for detection significant associations was applied as P < 1.2E × 10–6. The values for heritability were 0.036, 0.063, 0.035, and 0.068 for GL, CI, CR, and DI, respectively. Frequencies of the late abortions and stillbirths were 1.7 and 3.6% respectively. We identified some SNP with direct significant effects for fertility-related traits: BTA-31636-no-rs on BTA1 for GL (P = 1.2E × 10–6), Hapmap26774-BTA-163037 on BTA27 for CI (P = 1.1E × 10–6), and ARS-BFGL-NGS-89711 on BTA27 for CR (P = 2.1E × 10–7). One SNP (ARS-BFGL-NGS-92135) was found on BTA10 that was close to being significant for DI (P = 2.8E × 10–6). The direct EBV effect of SNP (R2) ranged from 8.4 to 9.0% of additive genetic variances. Genotyping bulls for LoF mutations revealed carrier frequencies of 2.0% for BY, 2.0% for HH1, and 4.3% for HH3. Our results will be useful to improve cow fertility traits in Holstein dairy herds in Russia. Furthermore, they allow selection of donor cows and bulls with more reliable EBV for fertility-related traits and that are free of LoF mutations associated with embryonic death for application in embryo transfer programs. The study was supported by the Federal Agency for Scientific Organizations and by the Russian Ministry of Education and Science, project no. RFMEFI60414X0062.

132 OVERVIEW OF FERTILITY TRAITS IN RUSSIAN HOLSTEIN BULLS USING GENOME-WIDE ASSOCIATION

2017 ◽  
Vol 29 (1) ◽  
pp. 174 ◽  
Author(s):  
A. A. Sermyagin ◽  
E. N. Naryshkina ◽  
E. A. Gladyr ◽  
I. N. Yanchukov ◽  
G. Brem ◽  
...  
Keyword(s):  
Semen Quality ◽  
Additive Genetic Variance ◽  
Sperm Concentration ◽  
Cattle Breed ◽  
Ministry Of Education ◽  
Data Set ◽  
Scientific Organizations ◽  
Estimated Breeding Values ◽  
Genomic Regions ◽  
Fertility Traits

Holsteins are the most widely distributed cattle breed in Russia. To achieve improvement of both milk production and fertility traits, principles were elaborated to use genomic approaches together with breeding strategies to develop a common breeding index. Combining semen-quality measures for sires with the cows’ reproduction records makes it possible to resolve the problems with decreased conception rates and semen production. Our objective was to search the genomic regions and associated markers for bulls’ fertility traits in Russian Holstein cattle. For the first step, 282 bulls were genotyped using the Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA, USA). The data set originated from the Moscow AI station including records for semen volume (SV), sperm concentration (SC), average SV for multiple ejaculates collected from one sire (ASV), motility (Mt), and number of spermatozoa (NS). The data set consisted of 14,490 records, which varied between 10 and 328 per animal, with 104 sires in the data set. The average age of sires was 80.1 ± 0.3 months. For sires with own records, the deregressed estimated breeding values were calculated using BLUP AM, whereas for the sires without records direct genomic values (DGV) were calculated through GBLUP. The DGV values were used as the animal’s pseudo-phenotypes for a common data set. After quality check in Plink 1.07, 41,435 SNP were taken. Bonferroni correction test for detection of significant associations was applied as P < 1.21 × 10−6. The values for the heritability were 0.322, 0.202, 0.366, 0.014, and 0.169 for SV, SC, ASV, Mt, and NS, respectively. The SNP with a direct significant effect on SV and ASV were identified: ARS-BFGL-NGS-100206 (P = 1.5 × 10−7), BTA-89872-no-rs (P = 6.0 × 10−8), ARS-BFGL-NGS-33119 (P = 2.7 × 10−7), Hapmap26947-BTA-133787 (P = 5.0 × 10−7), BTA-30092-no-rs (P = 9.8 × 10−7), ARS-BFGL-BAC-6515 (P = 1.0 × 10−7), and BTB-01625220 (P = 4.2 × 10−8). For SC and NS traits, the polymorphisms ARS-BFGL-NGS-57433 (P = 7.4 × 10−7) and ARS-BFGL-NGS-12662 (P = 5.1 × 10−7) were found. Two QTL for Mt including 11 SNP were detected on BTA1 (146.3–146.9 Mb) and BTA9 (76.9–77.1 Mb). The DGV effect of SNP (R2) ranged from 8.0 to 10.4% of additive genetic variance. The genes SOX5 (BTA12), PERP (BTA9), and EPT1 (BTA11) were associated with embryonic development, cell death, or apoptosis and synthesis of selenoproteins. Our results may be used to select donor cows for oocytes or embryo collection in the focus of genomic selection. Supported by the Federal Agency for Scientific Organizations #0600–2014–0007.6 and by the Russian Ministry of Education and Science #RFMEFI60414X0062.

scholarly journals Milk Yield, Reproduction and Milk Quality Characteristics of Simmental and Red-Holstein Cattle Raised in a Dairy Farm in Aydın Province: 1. Reproduction and Milk Yield

2020 ◽  
Vol 8 (10) ◽  
pp. 2068-2073
Author(s):  
Atakan Koç ◽  
Çağrı Arı
Keyword(s):  
Milk Yield ◽  
Dairy Farm ◽  
Quality Characteristics ◽  
Gestation Length ◽  
Peak Time ◽  
Holstein Cattle ◽  
Yield Traits ◽  
Lactation Length ◽  
Days Open ◽  
Fertility Traits

In this study, fertility and milk yield characteristics of Simmental (SIM) and Red-Holstein (RH) cattle raised in a private dairy farm in Aydın province were determined. For fertility traits, days open (DO), calving interval (CI), gestation length (GL) and number of inseminations per pregnancy (NIPP), for milk yield traits lactation length (LL), lactation milk yield (LMY), 305-days milk yield (305-dMY), peak time (PT) and peak milk yield (PMY) were determined. The means of DO, CI, GL and NIPP of RH and SIM breeds were 109.44±5.66 d and 96.06±3.51 d, 389.16±5.70 d and 380.37±3.54 d, 279.71±0.469 d and 284.94±0.303 d, 1.88±0.099 and 1.85±0.065; the means of LL, LMY, 305-dMY, PT and PMY were 333.00±5.405 d and 322.72±3.233 d, 8235.32±148.099 kg and 7357.03±88.122 kg, 7628.78±109.148 kg and 6938.09±64.945 kg, 46.55±2.196 d and 44.46±1.218 d, and 34.68±0.567 kg and 31.47±0.314 kg, respectively. Although, significant fertility and milk yield differences were obtained between the breeds, the favorable performances of both SIM and RH breeds in terms of all features, considered as the environmental factors such as management-feeding-housing-herd management provided to animals in the farm were also suitable.

scholarly journals Genomic variation in the American pika: signatures of geographic isolation and implications for conservation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kelly B. Klingler ◽  
Joshua P. Jahner ◽  
Thomas L. Parchman ◽  
Chris Ray ◽  
Mary M. Peacock
Keyword(s):  
Genetic Variation ◽  
Genetic Structure ◽  
Sierra Nevada ◽  
Spatial Genetic Structure ◽  
Spatial Scales ◽  
Thermal Sensitivity ◽  
Genomic Variation ◽  
Genome Wide ◽  
A Genome ◽  
American Pika

Abstract Background Distributional responses by alpine taxa to repeated, glacial-interglacial cycles throughout the last two million years have significantly influenced the spatial genetic structure of populations. These effects have been exacerbated for the American pika (Ochotona princeps), a small alpine lagomorph constrained by thermal sensitivity and a limited dispersal capacity. As a species of conservation concern, long-term lack of gene flow has important consequences for landscape genetic structure and levels of diversity within populations. Here, we use reduced representation sequencing (ddRADseq) to provide a genome-wide perspective on patterns of genetic variation across pika populations representing distinct subspecies. To investigate how landscape and environmental features shape genetic variation, we collected genetic samples from distinct geographic regions as well as across finer spatial scales in two geographically proximate mountain ranges of eastern Nevada. Results Our genome-wide analyses corroborate range-wide, mitochondrial subspecific designations and reveal pronounced fine-scale population structure between the Ruby Mountains and East Humboldt Range of eastern Nevada. Populations in Nevada were characterized by low genetic diversity (π = 0.0006–0.0009; θW = 0.0005–0.0007) relative to populations in California (π = 0.0014–0.0019; θW = 0.0011–0.0017) and the Rocky Mountains (π = 0.0025–0.0027; θW = 0.0021–0.0024), indicating substantial genetic drift in these isolated populations. Tajima’s D was positive for all sites (D = 0.240–0.811), consistent with recent contraction in population sizes range-wide. Conclusions Substantial influences of geography, elevation and climate variables on genetic differentiation were also detected and may interact with the regional effects of anthropogenic climate change to force the loss of unique genetic lineages through continued population extirpations in the Great Basin and Sierra Nevada.

scholarly journals Anopheles gambiae Genome Conservation as a Resource for Rational Gene Drive Target Site Selection

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 97
Author(s):  
Nace Kranjc ◽  
Andrea Crisanti ◽  
Tony Nolan ◽  
Federica Bernardini
Keyword(s):  
Anopheles Gambiae ◽  
Data Storage ◽  
Genomic Variation ◽  
Malaria Vectors ◽  
Anopheles Coluzzii ◽  
Structural Constraints ◽  
Gene Drive ◽  
Genetic Traits ◽  
A Genome ◽  
Insight Into

The increase in molecular tools for the genetic engineering of insect pests and disease vectors, such as Anopheles mosquitoes that transmit malaria, has led to an unprecedented investigation of the genomic landscape of these organisms. The understanding of genome variability in wild mosquito populations is of primary importance for vector control strategies. This is particularly the case for gene drive systems, which look to introduce genetic traits into a population by targeting specific genomic regions. Gene drive targets with functional or structural constraints are highly desirable as they are less likely to tolerate mutations that prevent targeting by the gene drive and consequent failure of the technology. In this study we describe a bioinformatic pipeline that allows the analysis of whole genome data for the identification of highly conserved regions that can point at potential functional or structural constraints. The analysis was conducted across the genomes of 22 insect species separated by more than hundred million years of evolution and includes the observed genomic variation within field caught samples of Anopheles gambiae and Anopheles coluzzii, the two most dominant malaria vectors. This study offers insight into the level of conservation at a genome-wide scale as well as at per base-pair resolution. The results of this analysis are gathered in a data storage system that allows for flexible extraction and bioinformatic manipulation. Furthermore, it represents a valuable resource that could provide insight into population structure and dynamics of the species in the complex and benefit the development and implementation of genetic strategies to tackle malaria.

scholarly journals A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 643
Author(s):  
Thibaud Kuca ◽  
Brandy M. Marron ◽  
Joana G. P. Jacinto ◽  
Julia M. Paris ◽  
Christian Gerspach ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Homozygosity Mapping ◽  
Mendelian Inheritance ◽  
Large Animal Model ◽  
Large Animal ◽  
Loss Of Function ◽  
Protein Coding ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

scholarly journals Genomic Variation in IbA10G2 and Other Patient-Derived Cryptosporidium hominis Subtypes

2016 ◽  
Vol 55 (3) ◽  
pp. 844-858 ◽  
Author(s):  
Per Sikora ◽  
Sofia Andersson ◽  
Jadwiga Winiecka-Krusnell ◽  
Björn Hallström ◽  
Cecilia Alsmark ◽  
...  
Keyword(s):  
Parasite Burden ◽  
Genomic Variation ◽  
Loss Of Function ◽  
Oocyst Wall ◽  
Gene Encoding ◽  
Cryptosporidium Hominis ◽  
Content Type ◽  
Successful Isolation ◽  
Target Dna ◽  
Stool Samples

ABSTRACTIn order to improve genotyping and epidemiological analysis ofCryptosporidiumspp., genomic data need to be generated directly from a broad range of clinical specimens. Utilizing a robust method that we developed for the purification and generation of amplified target DNA, we present its application for the successful isolation and whole-genome sequencing of 14 differentCryptosporidium hominispatient specimens. Six isolates of subtype IbA10G2 were analyzed together with a single representative each of 8 other subtypes: IaA20R3, IaA23R3, IbA9G3, IbA13G3, IdA14, IeA11G3T3, IfA12G1, and IkA18G1. Parasite burden was measured over a range of more than 2 orders of magnitude for all samples, while the genomes were sequenced to mean depths of between 17× and 490× coverage. Sequence homology-based functional annotation identified several genes of interest, including the gene encodingCryptosporidiumoocyst wall protein 9 (COWP9), which presented a predicted loss-of-function mutation in all the sequence subtypes, except for that seen with IbA10G2, which has a sequence identical to theCryptosporidium parvumreference Iowa II sequence. Furthermore, phylogenetic analysis showed that all the IbA10G2 genomes form a monophyletic clade in theC. hoministree as expected and yet display some heterogeneity within the IbA10G2 subtype. The current report validates the aforementioned method for isolating and sequencingCryptosporidiumdirectly from clinical stool samples. In addition, the analysis demonstrates the potential in mining data generated from sequencing multiple whole genomes ofCryptosporidiumfrom human fecal samples, while alluding to the potential for a higher degree of genotyping withinCryptosporidiumepidemiology.

scholarly journals Endocrine Fertility Parameters—Genomic Background and Their Genetic Relationship to Boar Taint in German Landrace and Large White

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 231
Author(s):  
Ines Brinke ◽  
Christine Große-Brinkhaus ◽  
Katharina Roth ◽  
Maren Julia Pröll-Cornelissen ◽  
Sebastian Klein ◽  
...  
Keyword(s):  
Genetic Relatedness ◽  
Genetic Relationships ◽  
Young Male ◽  
Boar Taint ◽  
Genetic Progress ◽  
Large White ◽  
Genome Wide ◽  
A Genome ◽  
Different Origins ◽  
Fertility Traits

The surgical castration of young male piglets without anesthesia is no longer allowed in Germany from 2021. One alternative is breeding against boar taint, but shared synthesis pathways of androstenone (AND) and several endocrine fertility parameters (EFP) indicate a risk of decreasing fertility. The objective of this study was to investigate the genetic background between AND, skatole (SKA), and six EFP in purebred Landrace (LR) and Large White (LW) populations. The animals were clustered according to their genetic relatedness because of their different origins. Estimated heritabilities (h2) of AND and SKA ranged between 0.52 and 0.34 in LR and LW. For EFP, h2 differed between the breeds except for follicle-stimulating hormone (FSH) (h2: 0.28–0.37). Both of the breeds showed unfavorable relationships between AND and testosterone, 17-β estradiol, and FSH. The genetic relationships (rg) between SKA and EFP differed between the breeds. A genome-wide association analysis revealed 48 significant associations and confirmed a region for SKA on Sus Scrofa chromosome (SSC) 14. For EFP, the results differed between the clusters. In conclusion, rg partly confirmed physiologically expected antagonisms between AND and EFP. Particular attention should be spent on fertility traits that are based on EFP when breeding against boar taint to balance the genetic progress in both of the trait complexes.

scholarly journals Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1713 ◽  
Author(s):  
Timothy A. McKinsey ◽  
Thomas M. Vondriska ◽  
Yibin Wang
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Loss Of Function ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Epigenomic Regulation ◽  
Generation Sequencing ◽  
Epigenetic Processes

Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.

scholarly journals Spemann organizer transcriptome induction by early beta-catenin, Wnt, Nodal, and Siamois signals in Xenopus laevis

2017 ◽  
Vol 114 (15) ◽  
pp. E3081-E3090 ◽  
Author(s):  
Yi Ding ◽  
Diego Ploper ◽  
Eric A. Sosa ◽  
Gabriele Colozza ◽  
Yuki Moriyama ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Gene Signature ◽  
Dorsal Side ◽  
Beta Catenin ◽  
Loss Of Function ◽  
Spemann Organizer ◽  
Signature Genes ◽  
A Genome ◽  
Vertebrate Model ◽  
Chloride Treatment

The earliest event in Xenopus development is the dorsal accumulation of nuclear β-catenin under the influence of cytoplasmic determinants displaced by fertilization. In this study, a genome-wide approach was used to examine transcription of the 43,673 genes annotated in the Xenopus laevis genome under a variety of conditions that inhibit or promote formation of the Spemann organizer signaling center. Loss of function of β-catenin with antisense morpholinos reproducibly reduced the expression of 247 mRNAs at gastrula stage. Interestingly, only 123 β-catenin targets were enriched on the dorsal side and defined an early dorsal β-catenin gene signature. These genes included several previously unrecognized Spemann organizer components. Surprisingly, only 3 of these 123 genes overlapped with the late Wnt signature recently defined by two other groups using inhibition by Dkk1 mRNA or Wnt8 morpholinos, which indicates that the effects of β-catenin/Wnt signaling in early development are exquisitely regulated by stage-dependent mechanisms. We analyzed transcriptome responses to a number of treatments in a total of 46 RNA-seq libraries. These treatments included, in addition to β-catenin depletion, regenerating dorsal and ventral half-embryos, lithium chloride treatment, and the overexpression of Wnt8, Siamois, and Cerberus mRNAs. Only some of the early dorsal β-catenin signature genes were activated at blastula whereas others required the induction of endomesoderm, as indicated by their inhibition by Cerberus overexpression. These comprehensive data provide a rich resource for analyzing how the dorsal and ventral regions of the embryo communicate with each other in a self-organizing vertebrate model embryo.

scholarly journals Fine mapping genetic variants associated with age at puberty and sow fertility using SowPro90 genotyping array

2020 ◽  
Vol 98 (10) ◽  
Author(s):  
Hiruni R Wijesena ◽  
Stephen D Kachman ◽  
Clay A Lents ◽  
Jean-Jack Riethoven ◽  
Melanie D Trenhaile-Grannemann ◽  
...  
Keyword(s):  
Litter Size ◽  
Genetic Variants ◽  
Research University ◽  
Genome Wide Association Study ◽  
Candidate Snps ◽  
Nucleotide Polymorphisms ◽  
Positional Candidate ◽  
Age At Puberty ◽  
Estimated Breeding Values ◽  
Fertility Traits

Abstract Sow fertility traits, such as litter size and the number of lifetime parities produced (reproductive longevity), are economically important. Selection for these traits is difficult because they are lowly heritable and expressed late in life. Age at puberty (AP) is an early indicator of reproductive longevity. Here, we utilized a custom Affymetrix single-nucleotide polymorphisms (SNPs) array (SowPro90) enriched with positional candidate genetic variants for AP and a haplotype-based genome-wide association study to fine map the genetic sources associated with AP and other fertility traits in research (University of Nebraska-Lincoln [UNL]) and commercial sow populations. Five major quantitative trait loci (QTL) located on four Sus scrofa chromosomes (SSC2, SSC7, SSC14, and SSC18) were discovered for AP in the UNL population. Negative correlations (r = −0.96 to −0.10; P &lt; 0.0001) were observed at each QTL between genomic estimated breeding values for AP and reproductive longevity measured as lifetime number of parities (LTNP). Some of the SNPs discovered in the major QTL regions for AP were located in candidate genes with fertility-associated gene ontologies (e.g., P2RX3, NR2F2, OAS1, and PTPN11). These SNPs showed significant (P &lt; 0.05) or suggestive (P &lt; 0.15) associations with AP, reproductive longevity, and litter size traits in the UNL population and litter size traits in the commercial sows. For example, in the UNL population, when the number of favorable alleles of an SNP located in the 3′ untranslated region of PTPN11 (SSC14) increased, AP decreased (P &lt; 0.0001), while LTNP increased (P &lt; 0.10). Additionally, a suggestive difference in the observed NR2F2 isoforms usage was hypothesized to be the source of the QTL for puberty onset mapped on SSC7. It will be beneficial to further characterize these candidate SNPs and genes to understand their impact on protein sequence and function, gene expression, splicing process, and how these changes affect the phenotypic variation of fertility traits.

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