As normal as normal can be?

Carter, Nigel P.

doi:10.1038/ng0904-931

Cited by 33 publications

(24 citation statements)

References 15 publications

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“…In addition, it is worth noting that expression levels can vary due to the presence of duplications in the genome. These duplications appear to vary between individuals and imply a diversity of loci across the genome, probably in a random manner, and resulting in copy number variations of the genes involved (Carter 2004;Iafrate et al 2004;Sebat et al 2004). A well characterized example of natural copy number variation is the gene for the CCL3-L1 chemokine that may vary in Caucasians from zero to six copies per diploid genome and which translates in a corresponding increase in the expression of this chemokine in vivo (Townson et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Increased gene dosage ofInk4a/Arfresults in cancer resistance and normal aging

Matheu¹,

Pantoja²,

Efeyan³

et al. 2004

Genes Dev.

126

121

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Mammalian genes frequently present allelic variants that differ in their expression levels and that, in the case of tumor suppressor genes, can be of relevance for cancer susceptibility and aging. We report here the characterization of a novel mouse model with increased activity for the Ink4a and Arf tumor suppressors. We have generated a "super Ink4a/Arf" mouse strain carrying a transgenic copy of the entire Ink4a/Arf locus. Cells derived from super Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation. Importantly, super Ink4a/Arf mice manifest higher resistance to cancer compared to normal, nontransgenic, mice. Finally, super Ink4a/Arf mice have normal aging and lifespan. Together, these results indicate that modest increases in the activity of the Ink4a/Arf tumor suppressor result in a beneficial cancer-resistant phenotype without affecting normal viability or aging.[Keywords: Ink4a; Arf; tumor suppression; stress; cancer resistance; aging; senescence] Supplemental material is available at http://www.genesdev.org.

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Section: Discussionmentioning

confidence: 99%

Increased gene dosage ofInk4a/Arfresults in cancer resistance and normal aging

Matheu¹,

Pantoja²,

Efeyan³

et al. 2004

Genes Dev.

126

121

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“…On average, 11 CNVs (Sebat et al 2004) or 12.4 CNVs (Iafrate et al 2004) were detected in each person with these array CGH assays. Initial commentaries (Carter 2004;Cheung 2004;Buckley et al 2005) noted the low overlap that appeared to exist between the data sets of these two studies. However, when the CNVs were mapped onto the same build of the human genome, more overlap of the two data sets could be appreciated with CNVs of larger size and frequency ( Table 2).…”

Section: Cnvs In Normal Individualsmentioning

confidence: 99%

Copy number variation: New insights in genome diversity

et al. 2006

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DNA copy number variation has long been associated with specific chromosomal rearrangements and genomic disorders, but its ubiquity in mammalian genomes was not fully realized until recently. Although our understanding of the extent of this variation is still developing, it seems likely that, at least in humans, copy number variants (CNVs) account for a substantial amount of genetic variation. Since many CNVs include genes that result in differential levels of gene expression, CNVs may account for a significant proportion of normal phenotypic variation. Current efforts are directed toward a more comprehensive cataloging and characterization of CNVs that will provide the basis for determining how genomic diversity impacts biological function, evolution, and common human diseases.

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“…Those affecting non-coding stretches of DNA may have little or no effect, but if the duplications or deletions include genes, then the CNV is likely to have functional consequences. CNVs could potentially account for individual differences, but on the other hand, the fact they are common in the general population means that it would be dangerous to assume that a particular CNV found in an individual necessarily plays a role in their disorder [34].…”

Section: (A) Rare Variants and Copy Number Variantsmentioning

confidence: 99%

The interface between genetics and psychology: lessons from developmental dyslexia

Bishop

2015

Proc. R. Soc. B.

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Developmental dyslexia runs in families, and twin studies have confirmed that there is a substantial genetic contribution to poor reading. The way in which discoveries in molecular genetics are reported can be misleading, encouraging us to think that there are specific genes that might be used to screen for disorder. However, dyslexia is not a classic Mendelian disorder that is caused by a mutation in a single gene. Rather, like many other common disorders, it appears to involve combined effects of many genes and environmental factors, each of which has a small influence, possibly supplemented by rare variants that have larger effects but apply to only a minority of cases. Furthermore, to see clearer relationships between genotype and phenotype, we may need to move beyond the clinical category of dyslexia to look at underlying cognitive deficits that may be implicated in other neurodevelopmental disorders.

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As normal as normal can be?

Cited by 33 publications

References 15 publications

Increased gene dosage ofInk4a/Arfresults in cancer resistance and normal aging

Increased gene dosage ofInk4a/Arfresults in cancer resistance and normal aging

Copy number variation: New insights in genome diversity

The interface between genetics and psychology: lessons from developmental dyslexia

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