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Deep sequencing of a candidate region harboring the SOX 9 gene for the canine XX disorder of sex development
Author(s) -
NowackaWoszuk J.,
Szczerbal I.,
Pausch H.,
Hundi S.,
Hytönen M. K.,
Grzemski A.,
Flisikowski K.,
Lohi H.,
Switonski M.,
Szydlowski M.
Publication year - 2017
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/age.12538
Subject(s) - biology , sox9 , candidate gene , genetics , gene , disorders of sex development , testis determining factor , computational biology , gene expression , y chromosome
Summary A disorder of sex development ( DSD ) in dogs with female sex chromosomes (78, XX ), a lack of the SRY gene and the presence of testes or ovotestes is commonly diagnosed in numerous breeds. The molecular background of DSD is not fully recognized but has been linked to the copy number variation in the region harboring the SOX 9 gene. We applied a genome‐wide association study and targeted next‐generation sequencing techniques to compare DSD and normal female dogs. The genome‐wide association study did not indicate a significant chromosome region. Targeted next‐generation sequencing of a 1.5‐Mb region on canine chromosome 9 harboring the SOX 9 gene revealed two putatively DSD ‐associated copy number variations 355 kb upstream and 691 kb downstream of SOX 9 , four blocks of low polymorphism and two blocks of an elevated heterozygosity. An initial next‐generation sequencing analysis showed an association with two SNP s, but validation in larger cohorts did not confirm this result. We identified a large homologous fragment (over 243.8 kb), named hf MAGI 2 , located upstream of SOX 9 , that overlaps a known copy number variation region. It shows a high sequence similarity with the 5′ flanking region of the MAGI 2 gene located on canine chromosome 18 that encodes a protein involved in ovary formation during early embryonic development. Our study showed that the identified copy number variation region located upstream of the SOX 9 gene contains potential regulatory sequences (long non‐coding RNA and hf MAGI 2 ) and led to the assumption that a multiplication of this element may alter expression of the SOX 9 gene, triggering the DSD phenotype.