Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats

Abstract The genetic background of feline disorders of sex development (DSDs) is poorly understood. We performed comprehensive cytogenetic, molecular, and histological studies of 17 cats with abnormal external genitalia, unusual behavior, or tricolor coats (atypical in males). The DSD phenotype of t...

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Main Authors: Monika Stachowiak, Izabela Szczerbal, Joanna Nowacka-Woszuk, Tomasz Nowak, Natalia Sowinska, Anna Lukomska, Maciej Gogulski, Malgorzata Badura, Karolina Sklorz-Mencel, Dariusz Jagodka, Wojciech Nizanski, Stanislaw Dzimira, Marek Switonski
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-21718-y
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author Monika Stachowiak
Izabela Szczerbal
Joanna Nowacka-Woszuk
Tomasz Nowak
Natalia Sowinska
Anna Lukomska
Maciej Gogulski
Malgorzata Badura
Karolina Sklorz-Mencel
Dariusz Jagodka
Wojciech Nizanski
Stanislaw Dzimira
Marek Switonski
author_facet Monika Stachowiak
Izabela Szczerbal
Joanna Nowacka-Woszuk
Tomasz Nowak
Natalia Sowinska
Anna Lukomska
Maciej Gogulski
Malgorzata Badura
Karolina Sklorz-Mencel
Dariusz Jagodka
Wojciech Nizanski
Stanislaw Dzimira
Marek Switonski
author_sort Monika Stachowiak
collection DOAJ
description Abstract The genetic background of feline disorders of sex development (DSDs) is poorly understood. We performed comprehensive cytogenetic, molecular, and histological studies of 17 cats with abnormal external genitalia, unusual behavior, or tricolor coats (atypical in males). The DSD phenotype of three cats was associated with sex chromosome abnormalities: X/Y translocation (38,XX SRY+), 37,X/38,XY mosaicism, and XX/XY leukocyte chimerism. The remaining 14 affected cats were classified as XY DSD (SRY-positive). In this group and 38 normal males, we analyzed a priori selected candidate genes (SRY, TAC3, CYP11B1 and LHCGR). Only a previously reported nonpathogenic variant was found in SRY. Moreover, SRY gene copy number was determined, and three variants were observed: 6, 5 (modal), and 4 copies in a single DSD case. The known variants in TAC3 and CYP11B1, responsible for testicular hypoplasia, persistent primary dentition or congenital adrenal hyperplasia, were not found in the study group. Nine novel polymorphisms were identified in the LHCGR gene, one of which, a potentially regulatory indel variant in 5′UTR, was significantly associated (p = 0.0467) with XY DSD. Our report confirmed that abnormalities of sex chromosomes are important causes of feline DSDs. We also showed that the indel variant of LHCGR can be considered a promising marker associated with XY DSD phenotype.
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spelling doaj.art-d1e1e53242144e24a9461c2b68bb76862022-12-22T04:33:08ZengNature PortfolioScientific Reports2045-23222022-10-0112111110.1038/s41598-022-21718-yCytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen catsMonika Stachowiak0Izabela Szczerbal1Joanna Nowacka-Woszuk2Tomasz Nowak3Natalia Sowinska4Anna Lukomska5Maciej Gogulski6Malgorzata Badura7Karolina Sklorz-Mencel8Dariusz Jagodka9Wojciech Nizanski10Stanislaw Dzimira11Marek Switonski12Department of Genetics and Animal Breeding, Poznan University of Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesDepartment of Preclinical Sciences and Infectious Diseases, Poznan University of Life SciencesDepartment of Preclinical Sciences and Infectious Diseases, Poznan University of Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesMencel-Vet Veterinary ClinicAura Veterinary ClinicDepartment of Reproduction and Clinic of Farm Animals, Wroclaw University of Environmental and Life SciencesDepartment of Pathology, Wroclaw University of Environmental and Life SciencesDepartment of Genetics and Animal Breeding, Poznan University of Life SciencesAbstract The genetic background of feline disorders of sex development (DSDs) is poorly understood. We performed comprehensive cytogenetic, molecular, and histological studies of 17 cats with abnormal external genitalia, unusual behavior, or tricolor coats (atypical in males). The DSD phenotype of three cats was associated with sex chromosome abnormalities: X/Y translocation (38,XX SRY+), 37,X/38,XY mosaicism, and XX/XY leukocyte chimerism. The remaining 14 affected cats were classified as XY DSD (SRY-positive). In this group and 38 normal males, we analyzed a priori selected candidate genes (SRY, TAC3, CYP11B1 and LHCGR). Only a previously reported nonpathogenic variant was found in SRY. Moreover, SRY gene copy number was determined, and three variants were observed: 6, 5 (modal), and 4 copies in a single DSD case. The known variants in TAC3 and CYP11B1, responsible for testicular hypoplasia, persistent primary dentition or congenital adrenal hyperplasia, were not found in the study group. Nine novel polymorphisms were identified in the LHCGR gene, one of which, a potentially regulatory indel variant in 5′UTR, was significantly associated (p = 0.0467) with XY DSD. Our report confirmed that abnormalities of sex chromosomes are important causes of feline DSDs. We also showed that the indel variant of LHCGR can be considered a promising marker associated with XY DSD phenotype.https://doi.org/10.1038/s41598-022-21718-y
spellingShingle Monika Stachowiak
Izabela Szczerbal
Joanna Nowacka-Woszuk
Tomasz Nowak
Natalia Sowinska
Anna Lukomska
Maciej Gogulski
Malgorzata Badura
Karolina Sklorz-Mencel
Dariusz Jagodka
Wojciech Nizanski
Stanislaw Dzimira
Marek Switonski
Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
Scientific Reports
title Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
title_full Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
title_fullStr Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
title_full_unstemmed Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
title_short Cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
title_sort cytogenetic and molecular insight into the genetic background of disorders of sex development in seventeen cats
url https://doi.org/10.1038/s41598-022-21718-y
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