Fine‑tuning genomic and pedigree inbreeding rates in equine population with a deep and reliable stud book:the case of the Pura Raza Española horse

Background:Estimating inbreeding,which is omnipresent and inevitable in livestock populations,is a primary goal for management and animal breeding especially for those interested in mitigating the negative consequences of inbreeding.Inbreeding coefficients have been historically estimated by using pedigree information;however,over the last decade,genome-base inbreeding coefficients have come to the forefront in this field.The Pura Raza Espanola(PRE)horse is an autochthonous Spanish horse breed which has been recognised since 1912.The total PRE population(344,718 horses)was used to estimate Classical(F),Ballou’s ancestral,Kalinowski’s ancestral,Kalinowski’s new and the ancestral history coefficient values.In addition,genotypic data from a selected population of 805 PRE individuals was used to determine the individual inbreeding coefficient using SNP-by-SNP-based techniques(methods of moments-FHOM-,the diagonal elements of the genomic-FG-,and hybrid matrixes-FH-)and ROH measures(FRZ).The analyse of both pedigree and genomic based inbreeding coefficients in a large and robust population such as the PRE horse,with proven parenteral information for the last 40 years and a high degree of completeness(over 90%for the last 70 years)will allow us to understand PRE genetic variability better and the correlations between the estimations will give the data greater reliability.Results:The mean values of the pedigree-based inbreeding coefficients ranged from 0.01(F for the last 3 generations-F3-)to 0.44(ancestral history coefficient)and the mean values of genomic-based inbreeding coefficients varied from 0.05(FRZ for three generations,FH and FHOM)to 0.11(FRZ for nine generations).Significant correlations were also found between pedigree and genomic inbreeding values,which ranged between 0.58(F3 with FHOM)and 0.79(F with FRZ).In addition,the correlations between FRZ estimated for the last 20 generations and the pedigree-based inbreeding highlight the fact that fewer generations of genomic data are required when comparing total inbreeding values,and the opposite when ancient values are calculated.Conclusions:Ultimately,our results show that it is still useful to work with a deep and reliable pedigree in pedigreebased genetic studies with very large effective population sizes.Obtaining a satisfactory parameter will always be desirable,but the approximation obtained with a robust pedigree will allow us to work more efficiently and economically than with massive genotyping.

Development of Genomic Microsatellite Multiplex PCR Using Dye-Labeled Universal Primer and Its Validation in Pedigree Analysis of Pacific Oyster(Crassostrea gigas)

There is an increasing requirement for traceability of aquaculture products, both for consumer protection and for food safety. There are high error rates in the conventional traceability systems depending on physical labels. Genetic traceability technique depending on DNA-based tracking system can overcome this problem. Genealogy information is essential for genetic traceability, and microsatellite DNA marker is a good choice for pedigree analysis. As increasing genotyping throughput of microsatellites, microsatellite multiplex PCR has become a fast and cost-effective technique. As a commercially important cultured aquatic species, Pacific oyster Crassostrea gigas has the highest global production. The objective of this study was to develop microsatellite multiplex PCR panels with dye-labeled universal primer for pedigree analysis in C. gigas, and these multiplex PCRs were validated using 12 full-sib families with known pedigrees. Here we developed six informative multiplex PCRs using 18 genomic microsatellites in C. gigas. Each multiplex panel contained a single universal primer M13(-21) used as a tail on each locus-specific forward primer and a single universal primer M13(-21) labeled with fluorophores. The polymorphisms of the markers were moderate, with an average of 10.3 alleles per locus and average polymorphic information content of 0.740. The observed heterozygosity per locus ranged from 0.492 to 0.822. Cervus simulations revealed that the six panels would still be of great value when massive families were analysed. Pedigree analysis of real offspring demonstrated that 100% of the offspring were unambiguously allocated to their parents when two multiplex PCRs were used. The six sets of multiplex PCRs can be an important tool for tracing cultured individuals, population genetic analysis, and selective breeding program in C. gigas.

OCCURRENCE CHARACTERISTIC OF KASHIN-BECK DISEASE BASED ON NUCLEAR FAMILY PEDIGREES

Objective The occurrence characteristic of Kashin Beck Disease (KBD) in pedigrees ascertained on the basis of one proband was estimated. Methods A total of 255 individuals in 40 pedigrees were collected from areas in the Shaanxi Province. Results ① Parents and siblings of index cases have a 3-4 times higher risk than a random unrelated individual. The odds ratio for disease is higher in mothers than in fathers of index cases; ② Prevalence in relatives of index cases (K r= 59.2% ) greatly exceeds population prevalence (K= 17.5% ); ③ K r increases with sibship size; ④ There is no significant difference of K r for male and female siblings of index cases. Also, population prevalence is not sex specific. Conclusion In conjunction with environmental agents, genetics may play an important role in KBD etiology.

Pedigree tracing of Fenneropenaeus chinensis by microsatellite DNA markers genotyping

Two microsateUite DNA loci were used to trace the pedigree structure of six families in the shrimp Fenneropenaeus chinensis. Four of the families were natural mating, and the others were mated by artificial insemination. Eleven alleles were acquired at two microsatellite DNA loci （locus RS0622 and locus EN0033 ） by investigating 145 offsprings and 11 parents. Five alleles were acquired from locus RS0622 and six from locus EN0033. As analyzed, the gene frequencies were between 0. 024 1 and 0. 493 1, the heterozygosity was 0.652 2 and 0.688 8, and the polymorphism information content （PIC） was 0.585 7 and 0.652 9 for the locus RS0622 and the locus EN0033, respectively. Twenty-three genotypes were detected and the genotypes of the losing parents were also inferred. The pedigrees of three F1 and three F2 generations were determined by matching the genotype at each locus.

Genetic relationship and pedigree of Chinese watermelon varieties based on diversity of perfect SNPs

Watermelon(Citrullus lanatus)is one of the world’s most important fruit crops,and China produces the most watermelons in the world.Recently,a watermelon variome consisting of 414 key resequenced accessions was reported.However,the genetic relationships and pedigree of Chinese watermelon varieties in the seed market remain unclear.In this study,241 evenly distributed perfect single nucleotide polymorphisms(SNPs)derived from the watermelon variome were selected for variety identification.The diversity of 247 Chinese watermelon varieties was identified based on their SNP genotypes.The 247 watermelon varieties were clustered into five subpopulations:the East Asian ecotype,intermediate ecotype,small fruit with red flesh ecotype,small fruit with yellow flesh ecotype,and American ecotype.We further established the pedigree of four subpopulations,of which JingXinNo.1,ZaoChunHongYu,HuangXiaoYu and XiaoLan,and Sugarlee were the main doner of the East Asian ecotype,small fruit with red flesh ecotype,small fruit with yellow flesh ecotype,and American ecotype,respectively.Thirty-two core SNPs were selected and applied in watermelon variety identification.They were also validated by the Kompetitive allele-specific PCR(KASPar)platform.The present study furthered our understanding of the genetic relationships and pedigree of watermelon varieties in China,and will help to manage the plant variety protection in watermelon.

POPULATION CHARACTERS IN HIGH RISK PEDIGREES OFNASOPHARYNGEAL CARCINOMA (NPC)

Objective: To investigate population characters in high risk pedigrees of NPC in Guangdong area and to explore the effect each other between tumor genetic susceptibility and infection of EB virus on pathogenic mechanism. Methods: Pedigree investigation, examination of DNA fingerprint, multi-antibodies of EB virus and nasopharyngeal cavity were done for all of the members in each high risk pedigree. Results: High positive rate of EBV VCA/IgA (23.22%), high percentage of high risk population of NPC (6.53–10.40%), high detected rate of malignant tumor (9552.59/105), and high detected rate of NPC (8464.32/105) were discovered and NPC was most common in first degree relative of a pedigree. Conclusion: Tumor genetic susceptibility, infection of EB virus might play a role in coordination of reinforced effect on occurrence of NPC.

Studies of a pedigree with limbal dermoid cyst

AIM: To study clinical features and gene mutations within the paired-like homeodomain transcription factor 2 (PITX2) gene in a pedigree of bilateral limbal dermoids. METHODS: Complete eye examinations have been performed on each individual of the family. Exons of paired-like homeodomain transcription factor 2 ( PITX2)were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: We described the phenotype, clinic findings in a family with two affected members. The masses of the proband's eyes were excised surgically demonstrating a dermoid cyst by histopathological examination. No mutation was detected in the gene PITX2 in this pedigree. CONCLUSION: A family of limbal dermoid cyst was reported. In addition, no pathogenic sequence variations were found in PITX2, indicating that this phenotype in this family is a distinctive entity.

Pedigree and SSR Data Analysis Reveal Dominant Prevalence of Few Parents in Pedigrees of Pakistani Wheat Varieties

The international recognition of the importance of genetic diversity demands continuous estimation of genetic diversity of in hand population as test of its buffering capacity against all putative threats. Randomly selected Pakistani wheat varieties developed during 1965-1999 and 2000-2011 were evaluated on the basis of pedigree and SSR data. At 2nd and 3rd levels of pedigree, average occurrence of a parent per variety was 2.1 times. The dominating parents included BLUEBIRD, KALYANSONA and SIETE-CERROS-66, which were present in the pedigrees of 71.42%, 64.28%, and 58.57% varieties, respectively. The varieties INQLAB-91 and KIRAN-95 had the same pedigree and were genetically identical as revealed by SSR data. Similarly, varieties PAVON-76 and SOGHAT-90 also had the same parents in their pedigrees. This genetic similarity was also confirmed by SSR based cluster. The SSR based PC1 and PC2 showed narrow genetic diversity confirming the presence of few dominating parents. The results emphasize the inclusion of novel and genetically diverse parents in Pakistani wheat breeding programs to maintain broader genetic base of varieties/cultivars for buffering the effects of ever changing virulent pathogens and crop growth environments.

Chromsome and pedigree analysis of congenital malformation of external and middle ear

Objective:Using chromosome analysis of a Chinese pedigree to investigate the genetic relationship between chromosome and congenital malformation of the external and middle ear combined with pre-auricular fistula.Methods: Clinical data of all members from 3 family with congenital malformation of the external and middle ear combined with pre-auricular fistula were collected. A pedigrees chart of each family was draw Venous blood samples of all participants were taken for karyotype analysis.Results: A total of 21 members in three generations from three families were screened. Chromosomal abnormalities were detected in 9 people, including 3 patients and 6 carriers. The carriers were fathers and paternal grandparents. Structural abnormalities in chromosomes 1, 2 and 11 were identified.Conclusion:The genetic patterns of congenital malformation of the external and middle ear combined with the pre- auricular fistula in these three families are consistent with autosomal recessive inheritance. Family survey is helpful for further study of this disease.

A Pedigree Analysis of a Family With Familial Hypercholesterolemia

Objective The current study was designed to investigate the features of a family with familial hypercholesterolemia(FH). Methods Twenty members of three generations in a family with FH were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. Results The proband was a 41 years old male who suffered from angina pectoris with multi-vessel stenosis of coronary artery at the age of 40. Among 20 members, 8 individuals were demonstrated with hypercholes-terolemia in this family with the total incidence of 40% [54.5% (6/11) in male and 22. 2% (2/9) in femaleThe serum total cholesterol level was elevated in childhood from 7. 1 to 10. 8 mmol/L and tended to be raised with increasing age. In addition, the level of total cholesterol was found to be elevated both in a monozy-gote twin brothers and their offspring in the family. Conclusion FH appears to be a hereditary disease of autosomal dominance inheritance and the outcome of FH patients with coronary heart disease seems to be poor in prognosis.

Genetic Diversity and Ancestral History of the German Angler and the Red-and-White Dual-Purpose Cattle Breeds Assessed through Pedigree Analysis

Local cattle breeds continue to decline in numbers partly due to the use of high performing breeds in advanced production systems where genetic material of elite animals is widely spread. The objective of this study was to assess the within and across breed genetic diversity of the Angler and Red-and-White dual-purpose (DP) cattle breeds applying different inbreeding concepts. Classical and ancestral inbreeding coefficients were computed from pedigree data using the gene dropping method. Effective population size was calculated based on the increase of classical inbreeding, and based on ancestral inbreeding to obtain what was termed as ancestral effective population size. Furthermore, the effective number of founders and ancestors were computed to assess the disequilibrium of founder contribution in the reference populations. The analyses were performed separately for each breed and for a combined dataset. The Angler pedigree was more complete (88%) in the first parental generation but completeness declined with increasing pedigree depth. Average classical inbreeding coefficients of inbred individuals were 2.19%, 1.94% and 2.07%, while average Ballou’s ancestral inbreeding coefficients were 3.69%, 1.39% and 2.21% for the Angler, Red-and-White DP and the combined breed pedigree analyses, respectively. Ancestral history coefficient is a novel coefficient and its estimates were similar and strongly correlated to Ballou’s coefficients (r = 0.99, p < 0.001). The effective population size estimates ranged from 156 to 170 for the classical inbreeding based method, and as low as from 50 to 54 for the ancestral history coefficient based method. The effective number of founders and ancestors ranged from 310 to 532, and 90 to 189, respectively. Our results show that the Red Holstein breed is a key progenitor of the breed populations under study. This highlights cross breeding schemes introduced to improve the milk trait performance of the Angler and Red-and-White DP breeds some decades ago.

RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A

Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three

Resulting of pedigree and topology of centripetal spatial schema in Chinese traditional cities

Chinese Traditional Maps and Local Chronicles serve as significant sources for investigating the urban history of ancient Chinese cities.These documents prioritize the abstract representation of topological relationships over precise numerical values and geometric shapes.This is consistent with the traditional Chinese city image and spatial schema emphasizing“harmony between man and nature”.Most Chinese Traditional Maps reflect a centripetal spatial schema,wherein the core area is located at the center,and other locations are positioned hierarchically about the center.Based on this data,this research aims to categorize and examine the development and evolution of the centripetal spatial schema in ancient Chinese cities by constructing a pedigree of types.The authors identify three types and summarize their causes,calculate the topological features,and reveal their correlations with the type of pedigree.This study reveals that cities with different centripetal forms exhibit regular differences in the accessibility,centrality,and functional attributes of central nodes,as well as the proportion of nodes with different attributes in the city.Overall,the conclusion aims to deepen people’s understanding of traditional Chinese spatial concepts at the macro-urban level,particularly in the context of China’s current urban renewal wave.Additionally,it provides practical references for inheriting and applying Chinese traditional construction wisdom.

Deciphering Starch Quality of Rice Kernels Using Metabolite Profiling and Pedigree Network Analysis

The physiological properties of rice grains are immediately obvious to consumers. High-coverage metabolomic characterization of the rice diversity research set predicted a negative correlation between fatty acid and lipid levels and amylose/total starch ratio （amylose ratio）, but the reason for this is unclear. To obtain new insight into the relationships among the visual phenotypes of rice kernels, starch granule structures, amylose ratios, and metabolite changes, we investigated the metabolite changes of five Japonica cultivars with various amylose ratios and two knockout mutants （e 1, a Starch synthase Ilia （SSIIla）-deficient mutant and the SSIIla/starch branching enzyme （BE） double-knockout mutant 4019） by using mass spectrometry-based metabolomics techniques. Scanning electron microscopy clearly showed that the two mutants had unusual starch granule structures. The metabolomic compositions of two cultivars with high amylose ratios （Hoshiyutaka and Yumetoiro） exhibited similar patterns, while that of the double-knockout mutant, which has an extremely high amylose ratio, differed. Rice pedigree network analysis of the cultivars and the mutants provided insight into the association between metabolic-trait properties and their underlying genetic basis in rice breeding in Japan. Multidimensional scaling analysis revealed that the Hoshiyutaka and Yumetoiro cultivars were Indica-like, yet they are classified as Japonica subpopulations. Exploring metabolomic traits is a powerful way to follow rice genetic traces and breeding history.

Efficient Haplotype Inference Algorithms in One Whole Genome Scan for Pedigree Data with Non-genotyped Founders

An efficient rule-based algorithm is presented for haplotype inference from general pedigree genotype data, with the assumption of no recombination. This algorithm generalizes previous algorithms to handle the cases where some pedigree founders are not genotyped, provided that for each nuclear family at least one parent is genotyped and each non-genotyped founder appears in exactly one nuclear family. The importance of this generalization lies in that such cases frequently happen in real data, because some founders may have passed away and their genotype data can no longer be collected. The algorithm runs in O（m^3n^3） time, where m is the number of single nucleotide polymorphism （SNP） loci under consideration and n is the number of genotyped members in the pedigree. This zero-recombination haplotyping algorithm is extended to a maximum parsimoniously haplotyping algorithm in one whole genome scan to minimize the total number of breakpoint sites, or equivalently, the number of maximal zero-recombination chromosomal regions. We show that such a whole genome scan haplotyping algorithm can be implemented in O（m^3n^3） time in a novel incremental fashion, here m denotes the total number of SNP loci along the chromosome.

The Complexity of Checking Consistency of Pedigree Information and Related Problems

Consistency checking is a fundamental computational problem in genetics.Given a pedigree and information on the genotypes (of some) of the individuals in it, the aim ofconsistency checking is to determine whether these data are consistent with the classic Mendelianlaws of inheritance. This problem arose originally from the geneticists'' need to filter their inputdata from erroneous information, and is well motivated from both a biological and a sociologicalviewpoint. This paper shows that consistency checking is NP-complete, even with focus on a singlegene and in the presence of three alleles. Several other results on the computational complexity ofproblems from genetics that are related to consistency checking are also offered. In particular, itis shown that checking the consistency of pedigrees over two alleles, and of pedigrees withoutloops, can be done in polynomial time.

Revisiting the Evolutionary History of Pigs via De Novo Mutation Rate Estimation in A Three-generation Pedigree

The mutation rate used in the previous analyses of pig evolution and demographics was cursory and hence invited potential bias in inferring evolutionary history.Herein,we estimated the de novo mutation rate of pigs as 3.6×10-9 per base per generation using high-quality whole-genome sequencing data from nine individuals in a three-generation pedigree through stringent filtering and validation.Using this mutation rate,we re-investigated the evolutionary history of pigs.The estimated divergence time of~10 kiloyears ago(KYA)between European wild and domesticated pigs was consistent with the domestication time of European pigs based on archaeological evidence.However,other divergence events inferred here were not as ancient as previously described.Our estimates suggest that Sus speciation occurred~1.36 million years ago(MYA);European wild pigs split from Asian wild pigs only~219 KYA;and south and north Chinese wild pigs split~25 KYA.Meanwhile,our results showed that the most recent divergence event between Chinese wild and domesticated pigs occurred in the Hetao Plain,northern China,approximately 20 KYA,supporting the possibly independent domestication in northern China along the middle Yellow River.We also found that the maximum effective population size of pigs was~6 times larger than estimated before.An archaic migration from other Sus species originating~2 MYA to European pigs was detected during western colonization of pigs,which may affect the accuracy of previous demographic inference.Our de novo mutation rate estimation and its consequences for demographic history inference reasonably provide a new vision regarding the evolutionary history of pigs.

Assessment of the forensic application of 50 Y-STR markers in a large pedigree

Short tandem repeats on the Y chromosome(Y-STRs),characterized by paternal inheritance,are valuable in forensic practice.Notably,the potential application of Y-STRs in pedigrees should be drawn upon,especially in China’s surname-concentrated natural villages.The study focused on 50 Y-STRs,including 13 rapidly mutating(RM)Y-STRs that largely constitute the current Y-STR commercial kits,and determined the differences in these Y-STRs between branches in a large pedigree and the discriminatory power of these haplotypes in different units for male relatives.As indicated in the results,14 inconsistencies were observed at 9 Y-STRs between 10 father-son pairs.In addition,these 50 Y-STR haplotypes discriminated 10 out of 47 father-son pairs,106 of 148 cousin pairs,70 of 119 uncle-nephew pairs,17 of 39 brother pairs,and 14 out of 33 grandfather-grandson pairs in a large pedigree.The RM Y-STR set is able to differentiate close male relatives in a large pedigree.

AN INVESTIGATION OF PEDIGREES OF 110 PATIENTS WITH GRAVES' DISEASE AND THE CLINICAL SIGNIFICANCE OF DETERMINATIONS OF ANTITHYROID ANTIBODIES OF THEIR FIRST-DEGREE RELATIVES

Eight hundred and ten pedigree members of 110 patients with Graves' disease were studied. In 700 first-egree relatives, inquiry of medical history, physical examination (including eyes, thyroid, heart rate, etc), thyroid function tests (serum T3, T4 and TSH levels), determinations of thyroglobulin antibodies (TgAb) and thyroid microsomal antibodies (TmAb) were performed. For male (female) probands, the incidence of Graves' disease in male (female) first-degree relatives were investigated and their serum TgAb and TmAb were analysed. The incidence of these two kinds of autoantibodies in the male (female) first-egree relatives of familial and nonfamilial Graves' disease were analysed. Eighteen persons with positive TgAb and TmAb from 5 pedigrees had been followed up one year after initial determinations. Our results suggest that the positive rates of TgAb and TmAb in the first-egree relatives of Graves' disease were coincident with the incidence of Graves' disease, and the positive results of TgAb and TmAb in the first-egree relatives of Graves' disease may be an indicator of pre-raves' disease or pre-utoimmune thyroid diseases.