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Gene Duplication and Sequence Variants of the Rattus norvegicus Y‐Chromosome can Alter Kidney Function
Author(s) -
Prokop Jeremy,
Lazar Jozef,
Underwood Adam,
Jacob Howard
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.665.11
Subject(s) - biology , y chromosome , genetics , gene , chromosome , testis determining factor , gene duplication , chromosome 15 , chromosome 16 , spontaneously hypertensive rat , microbiology and biotechnology , chromosome 22 , chromosome 3 , blood pressure , endocrinology
The Y‐chromosome of mammals contributes to numerous diseases with sex disparities such as those of the cardiovascular system and renal function; however, development of model organisms to study these diseases is limited. Y‐chromosome consomics of the SHR or the SS rat strains result in altered kidney function, suggesting genetic contributions of the different rat stain Y‐chromosomes to disease development. Genetic analysis of the Y‐chromosome in whole genome sequencing of 18 male rat strains (including the SHR and SS) relative to 5 female rat strains has identified many genetic variants on the Y‐chromosome genes in addition to identifying 9 autosomal genes that have duplicated onto the rat Y‐chromosome. Analysis of RNAseq for ten tissues over four ages of the rat showed expression profiles ( u =ubiquitous expression, t =testis specific expression) for EIF2S3Y ( u ) , ZFY ( t ) , USP9Y ( t ) , DDX3Y ( u ) , UTY ( u ) , UBE1Y ( t ) , KDM5D ( u ) , RBMY ( t ), MED14Y (retroposed gene, u ) , UBE2Q2Y (retroposed gene, u ),and Sry (eight gene copies with an additional copy in the SHR strain, u ) . A variant (P76T) in the Sry3 gene copy (expressed in the kidney) is able to elevate blood pressure through regulation of the renin‐angiotensin system (elevation blocked with Olmesartan) and may be a contributing factor to the SHR Y‐chromosome blood pressure elevation. One of the most interesting observations made during our analysis of the Y‐chromosome genes in the rat was that 104 week old rats have an expression profile for Y‐chromosome genes that is significantly altered from that of the 21 week old rats (in both the testis and the kidney), suggesting correlations between aging and Y‐chromosome contributions to physiology.