Randy L. Jirtle, Ph.D.

Genistein methylates the fetal epigenome

Dolinoy, et. al. Environ Health Perspect 114:567-72 (2006)

Maternal dietary genistein supplementation of mice during gestation was shown in this paper to shift the coat color of Avy offspring from yellow to pseudoagouti by altering the epigenome rather than mutating the genome; a clear example of nature via nurture. Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States.

August 9, 2012Tweet

Genome-wide prediction of imprinted murine genes

Luedi, et. al. Genome Res 15:875-84 (2005)

A machine learning approach was used to both identify imprinted gene candidates and predict their parental expression preference across the entire mouse genome. This subset of genes is particularly important medically becasue imprinted genes could function as targets for linking environmental exposures during pregnancy to the susceptibility of developing chronic disorders as adults. Among those predicted to be imprinted are strong candidate genes for complex human conditions where parent-of-origin inheritance is involved, including Alzheimer disease, autism, bipolar disorder, diabetes, male sexual orientation, obesity, and schizophrenia.

August 9, 2012Tweet

Nobel symposium lecture

Dr Jirtle was invited to speak at the Nobel Symposium on Epigenetic Reprogramming in Development and Disease, held June 19-21, 2004 in Stockholm. He spoke on the “Biological Consequences of the Divergent Evolution of M6P/IGF2R Imprinting".

August 9, 2012Tweet

You are what your mother ate!

Waterland and Jirtle. Mol Cell Biol 23:5293-300 (2003)

Dietary supplementation with extra folic acid, vitamin B(12), choline, and betaine alters the phenotype of Agouti mouse offspring via increased CpG methylation, suggesting that dietary supplementation, long presumed to be purely beneficial, may have unintended deleterious influences on the establishment of epigenetic gene regulation in humans.

August 6, 2012Tweet

Callipyge mutation identified

Freking, et. al. Genome Res 12:1496-506 (2002)

A small genetic region near the telomere of ovine chromosome 18 was previously shown to carry the mutation causing the callipyge muscle hypertrophy phenotype in sheep. The mutation lies in a region of high homology among mouse, sheep, cattle, and humans, but not in any previously identified expressed transcript. Initial functional analysis indicates the sequence encompassing the mutation is part of a novel transcript expressed in sheep fetal muscle named CLPG1.

August 6, 2012Tweet

Divergent evolution in M6P/IGF2R imprinting: implications for cloning and cancer

Killian, et. al. Hum Mol Genet 10:1721-8 (2001)

M6P/IGF2R imprinting first appeared approximately 150 million years ago following the divergence of prototherian from therian mammals. Following this, M6P/IGF2R is imprinted in Artiodactyla, as it is in Rodentia and Marsupialia, but not in Scandentia, Dermoptera and Primates, including ringtail lemurs and humans. The absence of M6P/IGF2R imprinting in extant primates, due to its disappearance from the primate lineage over 75 million years ago, demonstrates that imprinting at this locus does not predispose to human disease. Moreover, the divergent evolution of M6P/IGF2R imprinting predicts that the success of in vitro embryo procedures such as cloning may be species dependent.

August 6, 2012Tweet

Marsupials and eutherians reunited

Killian, et. al. Mamm Genome 12:513-7 (2001)

The three living divisions of mammals are monotremes, marsupials and 'placental' mammals. Determining the sister relationships among these three groups is the most fundamental question in mammalian evolution. Statistical analysis of the M6P/IGF2R unambiguously supports the morphology-based Theria hypothesis of mammalian evolution that excludes monotremes from a clade of marsupials and eutherians.

August 6, 2012Tweet

Imprinting of PEG3

Murphy, et. al. Genomics 71:110-7 (2001)

The paternally expressed Peg3 gene in mice encodes an unusual Kruppel-type zinc finger protein implicated in critical cellular and behavioral functions including growth, apoptosis, and maternal nurturing behavior. The imprinted status of PEG3 throughout life coupled with its neural expression and putative roles in regulating cell growth suggests that PEG3 may be a susceptibility locus for cancer as well as neurobehavioral deficits.

August 6, 2012Tweet

M6P/IGF2R imprinting evolution in mammals

Killian, et. al. Mol Cell 5:707-16 (2000)

M6P/IGF2R is not imprinted in monotremes and does not encode for a receptor that binds IGF2. In contrast, M6P/IGF2R is imprinted in a didelphid marsupial, the opossum, but it strikingly lacks the element postulated to be involved in imprint control. Thus, invasive placentation and gestational fetal growth are not required for imprinted genes to evolve. These results also suggest that these two functions evolved in a mammalian clade exclusive of monotremes.

August 6, 2012Tweet