Complete Pedigree Research Articles

Inbreeding and pedigree analysis of the European red dairy cattle

BackgroundRed dairy cattle breeds have an important role in the European dairy sector because of their functional characteristics and good health. Extensive pedigree information is available for these breeds and provides a unique opportunity to examine their population structure, such as effective population size, depth of the pedigree, and effective number of founders and ancestors, and inbreeding levels. Animals with the highest genetic contributions were identified. Pedigree data included 9,073,403 animals that were born between 1900 and 2019 from Denmark, Finland, Germany, Latvia, Lithuania, the Netherlands, Norway, Poland, and Sweden, and covered 32 breeds. The numerically largest breeds were Red Dairy Cattle and Meuse-Rhine-Yssel.ResultsThe deepest average complete generation equivalent (9.39) was found for Red Dairy Cattle in 2017. Mean pedigree completeness ranged from 0.6 for Finncattle to 7.51 for Red Dairy Cattle. An effective population size of 166 animals was estimated for the total pedigree and ranged from 35 (Rotes Höhenvieh) to 226 (Red Dairy Cattle). Average generation intervals were between 5 and 7 years. The mean inbreeding coefficient for animals born between 1960 and 2018 was 1.5%, with the highest inbreeding coefficients observed for Traditional Angler (4.2%) and Rotes Höhenvieh (4.1%). The most influential animal was a Dutch Meuse-Rhine-Yssel bull born in 1960. The mean inbreeding level for animals born between 2016 and 2018 was 2% and highest for the Meuse-Rhine-Yssel (4.64%) and Rotes Hohenvieh breeds (3.80%).ConclusionsWe provide the first detailed analysis of the genetic diversity and inbreeding levels of the European red dairy cattle breeds. Rotes Höhenvieh and Traditional Angler have high inbreeding levels and are either close to or below the minimal recommended effective population size, thus it is necessary to implement tools to monitor the selection process in order to control inbreeding in these breeds. Red Dairy Cattle, Vorderwälder, Swedish Polled and Hinterwälder hold more genetic diversity. Regarding the Meuse-Rhine-Yssel breed, given its decreased population size, increased inbreeding and low effective population size, we recommend implementation of a breeding program to prevent further loss in its genetic diversity.

Impact and utility of shallow pedigree using single-step genomic BLUP for prediction of unbiased genomic breeding values.

In unstructured dairy programs, pedigree is usually shallow, which leads to biased prediction of breeding values using best linear unbiased prediction (BLUP). The objective of this study was to come out with a genomic prediction strategy that can utilize shallow pedigree information and predict unbiased and more accurate GEBV for sex-limited traits in a small population using single-step GBLUP (ssGBLUP). The data and models for a population under selection were simulated. Out of current 10 generations, 10th generation with 1000 candidates served as validation population. For the complete pedigree scenario, pedigree (P)BLUP estimated breeding values (EBV) were unbiased with accuracy (r) of 0.35 ± 0.02 and 0.26 ± 0.01 for 0.3 and 0.1 h2 scenario, respectively. For the shallow pedigree, biased prediction of breeding values and low accuracies were obtained with linear decline in the accuracy of EBV for removal of information on more distant pedigree. Accuracy and bias (ρ) for scenario with removing 4 distant generations from pedigree were 0.30 ± 0.02 and 0.55 ± 0.03, respectively, in moderate h2 scenario. Use of Genomic (G)BLUP, especially with "extreme phenotypic contrast selective genotyping," (TB) resulted in higher accuracy for a small reference of females; however, GEBV were highly biased. We observed that ssGBLUPF, where the numerator relationship matrix is corrected for inbreeding, resulted in more accurate and unbiased estimates of GEBV across shallow pedigree scenario, with TB all female reference (missing 4 distant generations: r = 0.50 ± 0.02; ρ = 0.96 ± 0.02). We recommend use of ssGBLUPF with two tailed selectively genotyped all female reference in shallow pedigree scenarios, to obtain unbiased and accurate GEBV for sex-limited traits, when resources are limited.

On the Gene Pool of Don Valley Grape Varieties

For the first time, 41 grape varieties of the Don Valley (Rostov oblast) are genotyped, for most of them complete pedigree was restored. Contrary to the widely held belief, most varieties are not related to the Vitis vinifera cultivars of Western Europe and Transcaucasia. Only two varieties (Pukhlyakovskiy Belyi and Moldavskiy) are identical with respect to the varieties Coarna Alba and Coarna Neagra from Romania (Moldova). The Pukhlyakovskiy Belyi variety has made a certain contribution to the gene pool of the Don Valley cultivars, which allows us to suppose selective breeding based on this variety. A significant contribution to the origin of the varieties of the region is made by the Crimean variety Kokur Belyi, North Caucasian Asyl Kara and Koz Ouzioum. Some varieties of the Don Valley have no known ancestors among the 932 studied cultivars of V. vinifera from all over the world. The research allows us to take a fresh look at the historical contacts of the peoples of Southern Russia; it also stimulates further genetic studies of grape cultivars in the North Caucasus and Crimea, including wild vines.

Variabilidade genética do gado Guzerat criado no norte do Brasil, com base na análise do pedigree

ABSTRACT Genealogical data comprised 45,711 animals born between 1901 and 2016, with 48,127 animals in the pedigree file. Population structure was analyzed in terms of pedigree completeness, individual inbreeding coefficient (F), generation interval (L), rate of inbreeding (ΔF), effective population size (Ne), effective number of founders (ff), and effective number of ancestors (fa). The herd initially consisted of 13 bulls and 14 cows, and there were variations in the number of selected bulls and cows throughout the analyzed period, with 2,575 bulls, 13,691 cows, and 45,711 births recorded at the end of 2016. In total, 48.81% of the cows had only one progeny. Most dams (47.59%) were between three and seven years old, with a mean L in the population of 7.9 years. According to the results, 52.75% of the cows, 44.92% of the bulls, and 63.71% of the calves of the Guzerat breed in the northern region of Brazil showed some degree of inbreeding, with small-magnitude coefficients (0.56, 0.83, and 0.71% for cows, bulls, and calves, respectively). This fluctuation did not hinder the genetic evolution of the herd in the region. The effective population size does not seem to compromise the maintenance of genetic variability in the breed.

Parent-offspring inference in inbred populations.

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obscure genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human data sets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called specific parent-offspring relationship estimation (spore). spore is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. spore therefore fills an important void in the arsenal of pedigree inference tools.

Effects of Selection on Breed Contribution in the Caballo de Deporte Español.

The equine breeding industry for sport's performance has evolved into a fairly profitable economic activity. In particular, the Caballo de Deporte Español (CDE) is bred for different disciplines with a special focus on Show Jumping. The main aim of this study was to determine the effects of 15 years of selection and to find out whether it has been effective and adequate regarding the CDE main breeding objectives. The whole pedigree of 19,045 horses registered as CDE was used, comprising 47,884 animals (18,799 males and 29,085 females). An analysis performed to check for the pedigree completeness level yielded a number of equivalent complete generations (t) equal to 1.95, an average generation interval (GI) of 10.87 years, mean inbreeding coefficient (F) of 0.32%, an average relatedness coefficient (AR) of 0.09% and an effective population size (Ne) of 204. For the analyses, animals were divided into fourteen breed groups. Additionally, in order to study the evolution of these breeds over time and their influence on CDE pedigree, five different periods were considered according to the year of birth of the animals. Performance data used in the analyses were the estimated breeding values (EBV) of the Show Jumping sport discipline of 12,197 horses in the CDE pedigree, available from the 2020 routine genetic evaluations of the CDE breeding program (starting in 2004). Dressage and Eventing EBV values were also assessed. Results showed values of F higher than expected under random mating; this pointed to some degree of inbred matings. With regard to the evolution of breeding values, we found that, in general, EBVs of offspring were higher than the EBVs of parents. Notwithstanding, there is still a need for improvement in population management and the coordination of the breeders to get higher responses but controlling the loss of genetic diversity in the CDE breed.

Prenatal Diagnosis and Management of Thrombocytopenia-Absent Radius Syndrome.

Prenatal Diagnosis and Management of Thrombocytopenia-Absent Radius Syndrome.

Changes in the genetic variability of the Furioso-North Star population between 1989 and 2019

The Furioso-North Star (FNS) is one of the indigenous Hungarian horse breeds, originated from Mezőhegyes Stud. The aim of this work was to analyze the pedigree diversity and inbreeding of the registered Hungarian Furioso-North Star population in two different time points: the first was the active population in 1989, the second was the active population in 2019. Pedigree data was analyzed using Endog 4.8 software. The pedigree completeness was calculated in three different ways. In the past 30 years the pedigrees became more complete. In the population 2019 were 5 horses with ancestor in the 40th generation. Only 17–17 animals covered the 50% of the genetic variability for the two population. The most important ancestor was Herod xx in both reference populations. The FNS breed has English Thoroughbred background, that might be the reason of having several horses form this breed in the database. There were six animals among the ten most important ancestors in both reference populations. The average inbreeding coefficient was 3.31 in 1989 and 4.22 in 2019. Animals with highest inbreeding coefficient were born from the mating of close relatives (typically father-daughter). The Bart Furioso III-84 Boglár had the highest inbreeding coefficient (0.299) in the population 2019.

Optimum contribution selection (OCS) analyses prompted successful conservation actions for Faroese Horse population

The Faroese horse, an endangered indigenous horse breed, is a part of the cultural and societal heritage of the Faroe Islands. Population history describes a severe bottleneck, prompting for quantification of the genetic diversity (level of inbreeding, probability of gene origin, effective population size) and assessment of sustainable conservation potential (Optimum Contribution Selection, OCS) of the Faroese horse population. The pedigree completeness (PCI) of the Faroese horse is adequate for a realistic estimation of the level of inbreeding (PCI5 = 0.96). In concordance with the known population history, the average inbreeding is exceptionally high; in the last cohort, it was equal to 26.8%. An estimate of the effective population size, based on individual increase in inbreeding and coancestry, accounting for the whole population history, was eight. OCS offers a tool to understand and control the increase in the average relationships in the population. Within a fixed number of matings, the repetitive use of stallions resulted in the lowest level of average relationships. Successful follow-up of mating schemes planned together with a holistic assessment of the suitability of an individual as a breeding candidate, will minimize the increase in inbreeding in future generations and maximize the possibility to increase the census size of the Faroese horse population.

On the modelling of weights of kids to enhance growth in a local goat population under Tunisian arid conditions: the maternal effects.

To provide the local goat population with an adequate breeding scheme under an arid environment, this study aimed to evaluate the use of alternative models attempting to dissect the additive genetic (AG) and permanent environmental (PE) components of direct and maternal effects on weights of kids up to weaning. Records of 903 local kids over a period of 16years were used in this study. Data were split into four groups corresponding to four periods along weight recording. Periods 1/2/3/4 contained weights in an interval with upper-lower limits of 1-20/25-60/65-120/125-150days of age. Models including or ignoring maternal genetic or permanent environmental effects were fitted for all traits. For all periods, the best models were those including the AG component for both direct and maternal effects and the direct PE effect. Heritability estimates of both the direct and maternal effects ranged from low (0.02 for maternal heritability in P1) to moderate (0.17 for direct and maternal heritability in P2 and P3). Period 1 showed the lowest values for heritability of both direct and maternal effects, with also the largest estimate of the ratio of residual to total variance (around 0.2) compared with the other periods, with decreasing ratios as age increased (from 0.13 for P2 to 0.07 for P4). Both direct and maternal estimated breeding values (EBVs) showed high correlations for models fitting direct AG and PE (DGP) effects. For direct EBVs (DEBVs), correlations were above 0.99, indicating that the same animals are expected to be selected under any model that includes those components, regardless of the maternal effects included. For maternal EBVs, correlations were also high, but slightly lower than for the DEBVs between models including DGP effects and maternal genetic effects. Overall, our recommendation for genetic evaluations of direct and maternal effects in this population raised in extensive and harsh conditions is to use weight records preferably collected during the period of high milk production of dams, for which direct and maternal effects are expected to show full expression. Complete pedigrees and several generations of dam-progeny recording are needed to obtain a proper separation of environmental and genetic components.

Pedigree-based analyses of changes in genetic variability in three major swine breeds in Taiwan after a disease outbreak.

Pedigree analysis was performed in three major Taiwanese swine breeds to evaluate the genetic variability in the current population and determine the main reason for genetic diversity (GD) loss after the occurrence of foot-and-mouth disease (FMD) in Taiwan. The pedigree files of the Duroc, Landrace, and Yorkshire breeds, containing 60,237, 87,177, and 34,373 records, respectively, were analyzed. We divided the population into two subpopulations (pre-1998 and post-1998) to determine the role of FMD in GD loss. Pedigree completeness and related indicators were analyzed to evaluate the pedigree quality, and several parameters were used to measure the levels of GD and further used to determine the major cause of GD loss. The pedigree completeness indexes for the different breeds were higher than 0.60, and the trend was enhanced after the FMD outbreak. The estimated proportion of random genetic drift in GD loss increased in all breeds over time (from 62.64% to 78.44% in Duroc; from 26.26% to 57.99% in Landrace; and from 47.97% to 55.00% in Yorkshire, respectively). The effective population size of Duroc and Landrace were increased by the time (Duroc: from 61.73 to 84.75; Landrace: from 108.70 to 113.64); however, it shows opposite trend in Yorkshire population (decline from 86.21 to 50.00). In summary, the occurrence of FMD led to the major loss of GD loss by random genetic drift. Therefore, for the recovery of GD, breeders in Taiwan should increase the effective population size with newly imported genetic materials and adjust the breeding strategy to reduce the inbreeding rate.

No evidence that grooming is exchanged for coalitionary support in the short- or long-term via direct or generalized reciprocity in unrelated rhesus macaques

Reciprocity is a prominent explanation for cooperation between non-kin. Studies designed to demonstrate reciprocity often focus on direct reciprocity in the timescale of minutes to hours, whereas alternative mechanisms like generalized reciprocity and the possibility of reciprocation over longer timescales of months and years are less often explored. Using a playback experiment, we tested for evidence of direct and generalized reciprocity across short and longer timescales. We examined the exchange of grooming for coalitionary support between unrelated female rhesus macaques in a population with a complete genetic pedigree. Females that received grooming were not more responsive to calls for coalitionary support from unrelated female group mates compared to control females that received agonism or no interaction — even when the call belonged to a females’ most recent grooming partner. Similarly, females were not more responsive to calls for support from their most frequent unrelated grooming partner of the last two years, nor if they received large amounts of grooming from all other females in their group. We interpret these results as an absence of evidence for direct or generalized reciprocity on any timescale in the exchange of grooming for coalitionary support in rhesus macaques. If grooming is exchanged for support in this population, it is with an intensity below our ability to detect it or over a longer timescale than we examined. We propose by-product explanations may also be at play and highlight the importance of investigating multiple mechanisms when testing apparently cooperative behaviors.Significance statementThe receipt of help can make some animals more likely to provide help in return, whether it be a singular act, or many acts accumulated over months. Similarly, the receipt of help, be it one act of aid, or a group’s worth of help over time, can make some animals more likely to pay help forward to others. Studies on Old World monkeys suggest females may give grooming and in return receive aid in future physical conflicts. Using a playback experiment, we found female rhesus macaques were not more responsive to calls for intervention in a simulated conflict after being groomed by unrelated females, even if the calling combatant was her most recent, or a long-time grooming partner. Our results suggest females in our study population may be receiving benefits other than support in conflicts for the grooming they provide.

Analyses of Genetic Diversity in the Endangered "Berrenda" Spanish Cattle Breeds Using Pedigree Data.

Simple SummaryThe two “berrenda” cattle breeds are important for the conservation of livestock genetic diversity in Spain. They have a great phenotypic and genotypic uniqueness and both of them are important from the cultural and the tourist perspectives. They also contribute to the conservation of the traditional “Dehesa” ecosystem. Both breeds are considered as endangered ones, but their genealogies have never been used for quantifying the risk status of their populations. The aim of this work was to monitor the structure of the “Berrenda en Negro” and the “Berrenda en Colorado” populations, their inbreeding rate and some other parameters that could be useful to prevent losses in their genetic diversity and to conduct and analyze the effect of the conservation programs developed by ANABE Breeders Association and finally, as a tool to implement some selective measures. We found that both “berrenda” cattle breeds retain a huge genetic variability from their founders’ populations, although they have been affected by a shallow depth in their pedigrees; as a consequence, we suggest increasing exchanges of breeding animals among herds, more specifically in the case of the “Berrenda en Negro” breed.Pedigree analyses of two endangered cattle breeds were performed in order to study the structure and the genetic variability in their populations. Pedigree data were analyzed from 12,057 individuals belonging to the “Berrenda en Negro” cattle breed (BN) and 20,389 individuals belonging to the “Berrenda en Colorado” cattle breed (BC) that were born between 1983 and 2020. BN and BC reference populations (RP) were set up by 2300 and 3988 animals, respectively. The generation interval in BN and BC reference populations was equal to 6.50 and 6.92 years, respectively. The pedigree completeness level was 82.76% in BN and 79.57% in BC. The inbreeding rates were 4.5% in BN and 3.4% in BC, respectively. The relationship among animals when they were born in different herds was 1.8% in BN and 5% in BC; these values increased to 8.5% and 7.7%, respectively when comparing animals that were born in the same herd. The effective number of founding herds was 23.9 in BN and 60.9 in BC. Number of ancestors needed to explain 50% of genes pool in the whole population was 50 and 101, in BN and in BC, respectively. The effective population size based on co-ancestries was 92.28 in BN and 169.92 in BC. The genetic variability has been maintained in both populations over time and the results of this study suggest that measures to promote the conservation of the genetic variability in these two breeds would go through for the exchange of breeding animals among farms and for monitoring the genetic contributions before implementing any selective action.

Genetic diversity, viability and conservation value of the global captive population of the Moroccan Royal lions.

This study evaluates the diversity of the so-called ‘Moroccan Royal lions’ using genealogical information. Lions are no longer extant in North Africa, but the previous wild population was an important element of the now-recognised northern subspecies (Panthera leo leo) that ranged across West Africa, North Africa and the Middle East into India. The remaining captive population of ‘Moroccan Royal lions’ seems to be significantly endangered by the loss of diversity due to the effective population size decrease. The pedigree file of this captive lion population consisted of 454 individuals, while the reference population included 98 animals (47 males and 51 females). The completeness of the pedigree data significantly decreased with an increasing number of generations. The highest percentage of pedigree completeness (over 70%) was achieved in the first generation of the reference population. Pedigree-based parameters derived from the common ancestor and gene origin were used to estimate the state of diversity. In the reference population, the average inbreeding coefficient was 2.14%, while the individual increase in inbreeding over generations was 2.31%. Overall, the reference population showed lower average inbreeding and average relatedness compared with the pedigree file. The number of founders (47), the effective number of founders (24) and the effective number of ancestors (22) were estimated in the reference population. The effective population size of 14.02 individuals confirms the critically endangered status of the population and rapid loss of diversity in the future. Thus, continuous monitoring of the genetic diversity of the ‘Moroccan Royal lion’ group is required, especially for long-term conservation management purposes, as it would be an important captive group should further DNA studies establish an affinity to P. leo leo.

Population structure of Marwari sheep through pedigree analysis

Marwari sheep breed is the main constituent of the migratory sheep flocks in the Rajasthan, India. The purpose of this research was to use pedigree data to evaluate population structure and genetic variability in a closed flock of Marwari sheep in Rajasthan, India. Pedigree information of 11,659 sheep lambed from 1981–2020 (39 years) in the closed flock of Marwari sheep reared at ICAR-CSWRI-ARC, Beechwal, Bikaner, Rajasthan, India were included in the analysis. Lambs born during 2017–2020 were considered as reference population. The mean of maximum generation (MG), complete generation (CG) and equivalent complete generation (EqG) was 9.12, 2.75 and 5.35, respectively. The completeness of pedigree was 92.70 % (1st generation), 83.03 % (2nd generation) and 73.79 % (3rd generation). Average inbreeding coefficient for animals in the whole and reference populations was 1.49 and 2.40 %, respectively. The average relationship coefficient for whole and reference population was 2.51 and 3.34 %, respectively. Mean generation interval (GI) were 3.5 and 3.3 years for whole and reference population. The realized effective population size was 87.17 for whole population. Effective numbers of founders (fe), ancestors (fa) and founder genome (fg) was 80, 46 and 16.76, respectively for reference population. The fe/fa ratio in the reference population was 1.74, indicating that bottlenecks had occurred. The genetic contribution of the 16 most powerful ancestors represented half of the genetic variability in the reference population. The findings showed that there were proofs of bottleneck and genetic drift however, there was also considerable genetic diversity present in the population. The continuous flow of genes has contributed to the maintenance of genetic variability in the closed flock reflecting that management was in right direction in the Marwari sheep nucleus flock.

500 years of breeding in the Carthusian Strain of Pura Raza Español horse: An evolutional analysis using genealogical and genomic data

The Carthusian horse is a Pura Raza Español (PRE) strain (CS), bred as a closed population since its creation more than 500years ago. The aim of this study was to analyse for the first time its population structure and situation of variability combining both genealogical (GEL) and genomic (GEN) data. The GEL data comprised 348,429 pedigree records (56,105 CS horses), while the GEN analysis included the high-density genotypes (670,804 SNPs) of 287 horses. Pedigree completeness demonstrated its accuracy, showing a good correlation of GEL (F) and GEN (FROH ) inbreeding coefficient in the case of PRE subpopulations partially related and non-related to Carthusian strain (0.68) but a lower value in the 100% Carthusian horses (0.42), due to the high weight of founders not detected by GEL analysis. GEN (PCA, AMOVA, and Admixture) and GEL analysis showed a good differentiation of subpopulations, but also a high level of introgression of the CS in the breed during past decades. A recent change in this trend was noteworthy, with a considerable reduction in CS variability and a genetic bottleneck (effective population sizes of 31.57 and 30.20 in GEL and GEN analysis, respectively, in last generation). The PRE has maintained its variability, and a considerable difference in estimated Ne by GEL (60.77) and GEN (188.0) data was observed. Using two sources of complementary information, it was found the existence of an ancient PRE strain with a unique genetic landmark, practically free from the influence of other equine populations.

Monitoring inbreeding and selection on scrapie resistance in a closed nucleus of Florina sheep breed

This study aims to investigate the impact of selection on scrapie resistance on the genetic variability of Florina sheep breed closed nucleus at the Research Institute of Animal Science, in the region of Central Macedonia, Greece. The complete pedigree dataset of the nucleus flock was used in the study, and the prion protein (PrP) gene polymorphisms were identified for each animal. Three annual selection regimes were simulated, where the selection of the rams and ewes for mating was based on the coancestry value between them and their PrP gene polymorphism. The population structure and pedigree were analyzed to assess the impact of selection on scrapie on the evolution of inbreeding and the effective population size.

ESTIMATE OF GENETIC COMPONENTS OF BIRTH WEIGHT USING MULTI-BREED MODELS WITH DIFFERENT PEDIGREE STRUCTURES IN MESTIZO SHEEP

The objectives of this paper were to verify the influence of the multi-breed model and pedigree structure in the estimates of the genetic components to birth weight in a mestizo herd. Using 1234 birth weight records in two ways, one dataset with complete pedigree information (n = 1028) and another with incomplete pedigree information (n = 1234). The pedigree was composed for 10 sires, 366 and 448 dams for complete and incomplete pedigree, respectively. Used for analysis the maximum restricted likelihood method about the animal model, considering the birth weight trait, for a dataset with or not complete pedigree, used the WOMBAT program. The direct heritability coefficients in both datasets did not present large difference, 0.06 and 0.09 to best models in the complete and incomplete pedigree, respectively. However, in the incomplete pedigree, the maternal heritability was 0.29. The residual variance, which on the best model of the dataset with complete pedigree presented 0.51 and 0.35 for the best model of the dataset with incomplete pedigree. Concluding, we find the influence of de multi-breed model only in the dataset with complete pedigree, that considered the direct and breed effects. In the dataset with incomplete pedigree, the better model was that considered the direct and maternal additive effects.

Assessing Genetic Diversity and Estimating the Inbreeding Effect on Economic Traits of Inner Mongolia White Cashmere Goats Through Pedigree Analysis.

Objective: The purpose of this study was to discover the population structure and genetic diversity of Inner Mongolia White Cashmere goats (IMCGs) and demonstrate the effect of inbreeding on the live body weight (LBW), cashmere yield (CY), fiber length (FL), and fiber diameter (FD) of IMCGs.Materials and Methods: All data were collected from pedigree information and production performance records of IMCGs from 1983 to 2019. The population structure and genetic diversity were analyzed by Endog 4.8 software. Inbreeding coefficients were obtained by the pedigree package in R. Then, a linear regression model was used to analyze how inbreeding influences economic traits in IMCGs. Four levels of inbreeding coefficients (Fi) were classified in this study, including Fi = 0, 0< Fi ≤ 6.25, 6.25< Fi ≤ 12.5 and Fi≥12.5. Variance analysis was performed to determine whether inbreeding levels had a significant effect on economic traits in IMCGs.Results: The proportions of rams and dams in IMCGs for breeding were relatively small, with values of 0.8 and 20.5%, respectively. The proportion of inbred animals in the entire population was high, with values up to 68.6%; however, the average inbreeding coefficient and relatedness coefficient were 4.50 and 8.48%, respectively. To date, the population has experienced 12 generations. The average generation interval obtained in the present study was 4.11 ± 0.01 years. The ram-to-son pathway was lowest (3.97 years), and the ewe-to-daughter pathway was highest (4.24 years). It was discovered that the LBW, CY, and FL increased by 3.88 kg, 208.7 g, and 1.151 cm, respectively, with every 1% increase in the inbreeding coefficient, and the FD decreased by 0.819 μm with every 1% increase in the inbreeding coefficient. Additionally, multiple comparison analysis indicated that when the inbreeding coefficient was higher than 6.25%, the LBW showed an obvious decreasing trend. The threshold value of inbreeding depression in the CY is 12.5%. However, inbreeding depression has not been observed in the FL and FD.Conclusion: Pedigree completeness needs to be further strengthened. The degree of inbreeding in this flock should be properly controlled when designing breeding programs.

Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study.

The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling.We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed.Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy.The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses.Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy.