Genetics: Identical twins not so similar
-
Mirror image: Identical twins are believed to be genetically identical, but one twin can have mutations not shared by the other.
Identical twins can be genetically different, which could explain why they do not always share disorders such as schizophrenia or autism, according to a study published in March in PLoS One.
Identical twins develop from one fertilized egg, and so start out with the same genetic information from each parent. But only 48 percent of identical twins in the case of schizophrenia, and 60 percent in the case of autism, share the diagnosis. Environmental effects and epigenetic factors — differences in gene expression that do not alter the DNA sequence — could explain this phenomenon.
Several studies in the past few years have linked copy number variations, or CNVs — deletions or duplications of DNA — with both schizophrenia and autism.
In 2009, researchers proposed the controversial hypothesis that mutations that occur after fertilization can also cause neurological disorders.
In the new study, the same research team looked at two pairs of discordant identical twins — meaning only one of the two children has schizophrenia — for CNVs.
The twins in one family have 15 spontaneous or de novo CNVs that are not inherited from their parents. Of the 15, 3 are present only in the twin with schizophrenia, and 7 only in the healthy twin. In the second family, 8 of 25 de novo CNVs are present only in the twin with schizophrenia and 7 are unique to the healthy twin.
Three of the de novo CNVs identified in this study — including one, 19q13.41, that is present in a twin with schizophrenia — are not listed in the database of genomic variants.
The DNA sequenced in the study is from blood, so it does not confirm that these genetic differences also exist in the brain. In both cases, the twin without schizophrenia has a diagnosed neurological disorder: bipolar disorder in one case and an episode of major depression in the other.
This article has been modified from the original. It has been changed to correct an error in the paper on the specifics of the de novo mutations.
Comments
Bearman and collegues have found the heritability of autism has been highly overestimated. see
Demography. 2010 May;47(2):327-43.
Social demographic change and autism.
Liu K, Zerubavel N, Bearman P.
SourcePaul F. Lazarsfeld Center for the Social Sciences, Columbia University, New York, NY 10027, USA.
Abstract
Parental age at child's birth--which has increased for U.S. children in the 1992-2000 birth cohorts--is strongly associated with an increased risk of autism. By turning a social demographic lens on the historical patterning of concordance among twin pairs, we identify a central mechanism for this association: de novo mutations, which are deletions, insertions, and duplications of DNA in the germ cells that are not present in the parents' DNA. Along the way, we show that a demographic eye on the rising prevalence of autism leads to three major discoveries. First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism.
PMID: 20608100 [PubMed - indexed for MEDLINE] PMCID: PMC3000023[Available on 2011/5/1]
Dear Ted,
This is indeed a very interesting study that suggests that environmental factors — such as paternal age — that increase the rate of de novo mutations would be concordant between monozygotic twins and so contribute to the heritability estimates. And it's true that the previous heritability estimates of ASD are based on small sample sizes.
The reasons for the increase in prevalence in autism are an ongoing question in the field, and we have covered Bearman's research in this area. See: <https://sfari.org/51/-/asset_publisher/6Tog/content/social-factors-may-drive-the-spike-in-autism-cases>
Also see the following article for a discussion of of a new study that underscores the importance of de novo mutations in autism. <https://sfari.org/news/-/asset_publisher/6Tog/content/family-sequencing-study-boosts-two-hit-model-of-autism>
Thank you for reading SFARI,
Jessica