Characterization of A Homozygous Deletion of Steroid Hormone Biosynthesis Genes in Horse Chromosome 29 as A Risk Factor for Disorders of Sex Development and Reproduction

Autor: Claire M. Wade, Brian W. Davis, Jay Jaxheimer, Dickson D. Varner, Charles C. Love, Terje Raudsepp, Caitlin Castaneda, Carolyn E. Arnold, Sharmila Ghosh, Maria K. Rosengren, Gabriella Lindgren, Matthew Jevit
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
disorders of sex development
medicine.medical_treatment
Reproductive health and childbirth
VARIANTS
Breeding
0302 clinical medicine
Animal and Dairy Science
Risk Factors
2.1 Biological and endogenous factors
ECA29
Disorders of sex development
Aetiology
Gonadal Steroid Hormones
20-ALPHA-HYDROXYSTEROID DEHYDROGENASE
Genetics (clinical)
Sequence Deletion
Genetics & Heredity
Genetics
education.field_of_study
Sexual Development
Homozygote
Single Nucleotide
Phenotype
FAMILY
horse
GENOME
Warmblood
AKR1C
Life Sciences & Biomedicine
cryptorchidism
lcsh:QH426-470
Genotype
Population
CNV
030209 endocrinology & metabolism
Biology
DIAGNOSIS
SEQUENCE
Polymorphism
Single Nucleotide
Chromosomes
Article
reproduction
03 medical and health sciences
medicine
Animals
Horses
Polymorphism
education
Gene
COPY NUMBER VARIATION
Whole genome sequencing
Science & Technology
COMPLEX
Human Genome
Chromosome
medicine.disease
Steroid hormone
lcsh:Genetics
030104 developmental biology
steroid hormone
BACKDOOR PATHWAY
Zdroj: Genes
Volume 11
Issue 3
Genes, Vol 11, Iss 3, p 251 (2020)
Genes, vol 11, iss 3
ISSN: 2073-4425
DOI: 10.3390/genes11030251
Popis: Disorders of sex development (DSD) and reproduction are not uncommon among horses, though knowledge about their molecular causes is sparse. Here we characterized a ~200 kb homozygous deletion in chromosome 29 at 29.7&ndash
29.9 Mb. The region contains AKR1C genes which function as ketosteroid reductases in steroid hormone biosynthesis, including androgens and estrogens. Mutations in AKR1C genes are associated with human DSDs. Deletion boundaries, sequence properties and gene content were studied by PCR and whole genome sequencing of select deletion homozygotes and control animals. Deletion analysis by PCR in 940 horses, including 622 with DSDs and reproductive problems and 318 phenotypically normal controls, detected 67 deletion homozygotes of which 79% were developmentally or reproductively abnormal. Altogether, 8&ndash
9% of all abnormal horses were homozygous for the deletion, with the highest incidence (9.4%) among cryptorchids. The deletion was found in ~4% of our phenotypically normal cohort, ~1% of global warmblood horses and ponies, and ~7% of draught breeds of general horse population as retrieved from published data. Based on the abnormal phenotype of the carriers, the functionally relevant gene content, and the low incidence in general population, we consider the deletion in chromosome 29 as a risk factor for equine DSDs and reproductive disorders.
Databáze: OpenAIRE
Externí odkaz: