An association and haplotype analysis of porcine maternal infanticide: A model for human puerperal psychosis?

Abstract

An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain.

Expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelium to esophageal cancer: Their differences and clinical significance

“…The FAM135B gene is located in chromosome 8 and has been reported to be differentially expressed in healthy people with tuberculosis (27), mental illness (39) and autism (40). To the best of our knowledge, Song et al (14) first reported that the FAM135B gene is a tumor-associated gene for esophageal cancer, by whole-genome sequencing and other technologies.…”

The pig X and Y chromosomes: structure, sequence and evolution

“…Many loci associated with mental retardation and brain function are found on the human X chromosome (Gécz et al 2009). We have previously shown an association of X-linked QTLs associated with maternal aggression in sows towards their young with puerperal psychosis in humans (Quilter et al 2007, 2012); this updated map of the pig X will make detecting significant loci and understanding their contribution to phenotypic traits far more robust in the future. These data also have relevance to the animal breeding industry; many of the QTLs mapped to the X chromosome are associated with production traits (e.g.…”

Understanding the pathophysiology of postpartum psychosis: Challenges and new approaches

“…Examination of hypothalamic gene expression in the maternal infanticide model identified multiple genes, the expression of which was altered in pigs showing aberrant behaviour; several of these mapped to the previously-implicated QTL regions [of particular note were the HTR2C (serotonin receptor 2C), DRD2 (dopamine receptor 2) and PRL (prolactin) genes, the first two encoding antipsychotic drug targets[29]]. A genome-wide association study in this model indicated candidate regions on porcine chromosomes 3, 4 and 15, syntenic with human chromosomal regions implicated in bipolar disorder and postpartum psychosis (including 16p13)[30], whilst a candidate gene association study suggested preliminary evidence for association with oestrogen receptor ( ESR1 ), excitatory amino acid transporter 2 ( EAAT2 ) and dopamine receptor 1 ( DRD1 ) genes, but not HTR2C [31]. …”