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 consequence...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.展开更多
Purpose:To analyze the hereditary modality of primary open-angle glaucoma in China.Methds:The genetic form of Pedigree GZ.1was analyzed using Mandalian hereditary rules.Results:PedigreeGZ.1 had following characteristi...Purpose:To analyze the hereditary modality of primary open-angle glaucoma in China.Methds:The genetic form of Pedigree GZ.1was analyzed using Mandalian hereditary rules.Results:PedigreeGZ.1 had following characteristics:1)The pedigree had four gene-rations,and there existed POAG patients in each generation;2)Each patient had a parent withPOAG.Ifthparents didn't suffer from the disease,their children would not.3)The incidence of POAG in the relatives of the patients was1/2,In addition,The age of onset,intraocular pressure,fundus and prognosis was different from each other in the patients.Conclusions:1)Pedigree GZ.1 is inherited as an autosomal dominant trait.2)There exists individual differences of clinical manifestations in POAG patients,Eye Science2000;16:53-55.展开更多
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 w...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.展开更多
AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundatio...AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.展开更多
BACKGROUND The pathophysiology of Fabry disease(FD)-induced progressive vital organ damage is irreversible.Disease progression can be delayed using enzyme replacement therapy(ERT).In patients with classic FD,sporadic ...BACKGROUND The pathophysiology of Fabry disease(FD)-induced progressive vital organ damage is irreversible.Disease progression can be delayed using enzyme replacement therapy(ERT).In patients with classic FD,sporadic accumulation of globotriaosylceramide(GL-3)in the heart and kidney begins in utero;however,until childhood,GL-3 accumulation is mild and reversible and can be restored by ERT.The current consensus is that ERT initiation during early childhood is paramount.Nonetheless,complete recovery of organs in patients with advanced FD is challenging.CASE SUMMARY Two related male patients,an uncle(patient 1)and nephew(patient 2),presented with classic FD.Both patients were treated by us.Patient 1 was in his 50s,and ERT was initiated following end-organ damage;this was subsequently ineffective.He developed cerebral infarction and died of sudden cardiac arrest.Patient 2 was in his mid-30s,and ERT was initiated when the patient was diagnosed with FD,during which the damage to vital organs was not overtly apparent.Although he had left ventricular hypertrophy at the beginning of this treatment,the degree of hypertrophy progression was limited to a minimal range after>18 years of ERT.CONCLUSION We obtained discouraging ERT outcomes for older patients but encouraging outcomes for younger adults with classic FD.展开更多
基金funded by the AGL-2017-84217-P Research project from Ministerio de Economia,Industria y Competitividad,Gobierno de Espana.
文摘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.
基金Supported by grants from Nature Science Fundation of China(No.39770789,39800163)Guangdong province (No.980112)
文摘Purpose:To analyze the hereditary modality of primary open-angle glaucoma in China.Methds:The genetic form of Pedigree GZ.1was analyzed using Mandalian hereditary rules.Results:PedigreeGZ.1 had following characteristics:1)The pedigree had four gene-rations,and there existed POAG patients in each generation;2)Each patient had a parent withPOAG.Ifthparents didn't suffer from the disease,their children would not.3)The incidence of POAG in the relatives of the patients was1/2,In addition,The age of onset,intraocular pressure,fundus and prognosis was different from each other in the patients.Conclusions:1)Pedigree GZ.1 is inherited as an autosomal dominant trait.2)There exists individual differences of clinical manifestations in POAG patients,Eye Science2000;16:53-55.
基金part of the research activities of the operational group,“Animal Genetic Resources”that operates under the auspices of the Agricultural European Innovation Partnership(EIP-AGRI)projectthe European Commission for providing funds for the project.
文摘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.
基金Supported by the Capital’s Funds for Health Improvement and Research (No.CFH.2020-2Z-5132)。
文摘AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.
基金Supported by the Red Cross Hospital Research and Training Fund,Fukushima R.C.Hosp.No.57.
文摘BACKGROUND The pathophysiology of Fabry disease(FD)-induced progressive vital organ damage is irreversible.Disease progression can be delayed using enzyme replacement therapy(ERT).In patients with classic FD,sporadic accumulation of globotriaosylceramide(GL-3)in the heart and kidney begins in utero;however,until childhood,GL-3 accumulation is mild and reversible and can be restored by ERT.The current consensus is that ERT initiation during early childhood is paramount.Nonetheless,complete recovery of organs in patients with advanced FD is challenging.CASE SUMMARY Two related male patients,an uncle(patient 1)and nephew(patient 2),presented with classic FD.Both patients were treated by us.Patient 1 was in his 50s,and ERT was initiated following end-organ damage;this was subsequently ineffective.He developed cerebral infarction and died of sudden cardiac arrest.Patient 2 was in his mid-30s,and ERT was initiated when the patient was diagnosed with FD,during which the damage to vital organs was not overtly apparent.Although he had left ventricular hypertrophy at the beginning of this treatment,the degree of hypertrophy progression was limited to a minimal range after>18 years of ERT.CONCLUSION We obtained discouraging ERT outcomes for older patients but encouraging outcomes for younger adults with classic FD.
