Monday, October 25, 2010

S1PR5 - Dad's diet and CNVs

A paper just out a couple weeks ago on the effects on beta cell gene expression in daughter rats due to the high-fat diet of their fathers has turned some attention of those who are interested in epigenetics to contributions from males. This is apt as many genes are known or predicted to be imprinted in human males.

One gene shown by Ng, et al. to be 1.23-fold down-regulated in beta cells of daughters whose fathers were fed a high-fat diet is S1pr5. In humans, S1PR5 encodes a sphingosine-1-phosphate receptor. The ligand of this receptor, lysosphingolipid sphingosine 1-phosphate (S1P), regulates cell proliferation, apoptosis, motility, and neurite retraction and its actions may be both intracellular as a second messenger and extracellular as a receptor ligand [RefSeq].

It is highly relevant that Glessner, et al. (2010) identified a CNV (copy number variant) in S1PR5 that associates with childhood obesity. That CNV is a deletion but whether this leads to down-regulation of S1PR5 is not known. That is likely but not a sure bet until experimental data are taken. Nonetheless, this is an interesting gene and may steal some of the spotlight that Ng, et al. shine on IL13RA2, the human ortholog of the rat gene showing the greatest fold-change in expression between daughter rats whose fathers were fed different diets.

Friday, October 22, 2010

Paternal-linked programming: High-fat diet and a daughter's obesity

A recent article by Ng, Morris, et al. describes a situation in rats where a father's high-fat diet promotes a phenotype relevant to obesity in the daughter offspring. There is also an interesting review of this report at Nutritional Blogma.

Here, I wished to point out that there are likely to be found many other examples of paternal-linked effects on offspring health. In this regard, Luedi, Hartemink, et al. published a list of computationally predicted instances of imprinting. Many of these are paternal in origin and some served as their training set. In all there are actually 71 genes with known or predicted paternal imprinting. I list those here:

APBA1 amyloid beta (A4) precursor protein-binding, family A, member 1 (X11)
BMP8A bone morphogenetic protein 8a
BRP44L brain protein 44-like
C9orf116 chromosome 9 open reading frame 116
C9orf85 chromosome 9 open reading frame 85
CCDC85A coiled-coil domain containing 85A
CDH18 cadherin 18, type 2
CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 (putative obesity gene (Tiffin, Hide 2006 Nucleic Acids Res. 34:3067))
DGCR6 DiGeorge syndrome critical region gene 6
DKFZp761D1918 hypothetical protein DKFZp761D1918
DLGAP2 discs, large (Drosophila) homolog-associated protein 2
DLK1 delta-like 1 homolog (Drosophila) (Constituitive expression of mouse Pref-1 (DLK1) inhibits, whereas anitsense Pref-1 enhances, 3T3-L1 adipocyte differentiation (Wang, Sul 2006 J Nutrition 136:2953))
EGFL7 EGF-like-domain, multiple 7
EVX1 even-skipped homeobox 1
FAM174A family with sequence similarity 174, member A
FAM59A family with sequence similarity 59, member A
FERMT2 fermitin family homolog 2 (Drosophila)
FLJ20464 hypothetical protein FLJ20464
FLJ25694 hypothetical protein FLJ25694
FLJ42875 FLJ42875 protein
FOXG1 forkhead box G1 (FOXG1 is implicated in epilepsy and Rett syndrome (Le Guen, Bienvenu, et al. 2010 Neurogenetics. in press; Pintaudi, Veneselli, et al. 2010 Epilepsy Behav. in press))
FUCA1 fucosidase, alpha-L- 1, tissue
GATA3 GATA binding protein 3 (Defects in GATA3 are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia)
GFI1 growth factor independent 1 transcription repressor
GNAS GNAS complex locus
HES1 hairy and enhancer of split 1, (Drosophila)
HYMAI hydatidiform mole associated and imprinted
IGF2 insulin-like growth factor 2 (somatomedin A)
IGF2AS insulin-like growth factor 2 antisense
INS insulin
IPW imprinted in Prader-Willi syndrome
ISM1 isthmin 1 homolog (zebrafish)
KBTBD3 kelch repeat and BTB (POZ) domain containing 3
L3MBTL l(3)mbt-like (Drosophila)
LDLRAP1 low density lipoprotein receptor adaptor protein 1 (genetic variants have been described affecting LDLRAP1 expression which associate with total cholesterol and LDL-C)
LOC51145 erythrocyte transmembrane protein
LY6D lymphocyte antigen 6 complex, locus D
MAGEL2 MAGE-like 2
MEST mesoderm specific transcript homolog (mouse) (MEST is a PPARG target; expression in adipose is 3-fold higher in control-fed vs under-nourished animals (Kozak Koza 2010 PLoS ONE 5:e11015))
MKRN3 makorin, ring finger protein, 3
MRAP2 melanocortin 2 receptor accessory protein 2
MYEOV2 myeloma overexpressed 2
NDN necdin homolog (mouse)
NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa
NKAIN3 Na+/K+ transporting ATPase interacting 3
NNAT neuronatin
NTM neurotrimin
OBSCN obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF
OR11L1 olfactory receptor, family 11, subfamily L, member 1
PEG10 paternally expressed 10 (upregulated in PI3K lung cancer pathway (Gustafson Spira 2010 Science Translational Medicine 2:26ra25))
PLAGL1 pleiomorphic adenoma gene-like 1
PRDM16 PR domain containing 16 (PRDM16 forms a transcriptional complex with the active form of CEBPB (C/EBP-beta, also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells (Kajimura, Spiegelman 2009 Nature))
PURG purine-rich element binding protein G
PYY2 peptide YY, 2 (seminalplasmin)
RBP5 retinol binding protein 5, cellular
SGCE sarcoglycan, epsilon
SIM2 single-minded homolog 2 (Drosophila)
SLC22A2 solute carrier family 22 (organic cation transporter), member 2 (identified in a GWAS for prostate cancer)
SNURF SNRPN upstream reading frame
SOX8 SRY (sex determining region Y)-box 8
SPON2 spondin 2, extracellular matrix protein
TIGD1 tigger transposable element derived 1
TMEM52 transmembrane protein 52
TMEM60 transmembrane protein 60
TNFRSF18 tumor necrosis factor receptor superfamily, member 18
TSHZ3 teashirt family zinc finger 3
WT1 Wilms tumor 1
ZIM2 zinc finger, imprinted 2 (ZIM2 shares 7 exons with PEG3 (Kim, Bergmann, Stubbs. 2000 Genomics. 64:114-8), which has been described as an obesity gene in mouse)
ZNF225 zinc finger protein 225
ZNF267 zinc finger protein 267
ZNF738 zinc finger protein 738

IGF2 and INS (insulin) are noted with interest given the Ng paper and its implications.