| 1. |
- Szatmari, Peter, et al.
(author)
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Mapping autism risk loci using genetic linkage and chromosomal rearrangements.
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328
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Journal article (peer-reviewed)abstract
- Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
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| 2. |
- Conde-Padin, P., et al.
(author)
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Revealing the mechanisms of sexual isolation in a case of sympatric and parallel ecological divergence
- 2008
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In: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 94:3, s. 513-526
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Journal article (peer-reviewed)abstract
- Two ecotypes of a marine intertidal snail (Littorina saxatilis), living at different microhabitats and shore levels, have evolved in sympatry and in parallel across the Galician rocky shore. These ecotypes differ in many traits (including size) due to differential adaptation. They meet, mate assortatively, and partially hybridize at the mid shore where the two microhabitats overlap. The partial sexual isolation observed is claimed to be a side-effect of the size differences between ecotypes combined with a size assortative mating found in most populations of this species. We investigated this hypothesis using three complementary experimental approaches. First, we investigated which of the different shell variables contributed most to the variation in individual sexual isolation in the field by using two new statistics developed for that purpose: (1) pair sexual isolation and (2) r(i), which is based on the Pearson correlation coefficient. We found that size is the most important trait explaining the sexual isolation and, in particular, the males appear to be the key sex contributing to sexual isolation. Second, we compared the size assortative mating between regions: exposed rocky shore populations from north-westwern Spain (showing incomplete reproductive isolation due to size assortative mating) and protected Spanish and Swedish populations (showing size assortative mating but not reproductive isolation between ecomorphs). Most of the variation in size assortative mating between localities was significantly explained by the within-population level of variation on size. Third, we performed a laboratory male choice experiment, which further suggested that the choice is made predominantly on the basis of size. These results confirm the mechanism proposed to explain the sexual isolation in the Galician hybrid zone and thus support this case as a putative example of parallel incipient speciation. (C) 2008 The Linnean Society of London.
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| 3. |
- den Hollander, F., et al.
(author)
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Bad configurations for random walk in random scenery and related subshifts
- 2005
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In: Stochastic Processes and their Applications. - : Elsevier BV. - 0304-4149. ; 115:7, s. 1209-1232
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Journal article (peer-reviewed)abstract
- In this paper we consider an arbitrary irreducible random walk on ℤd, d ≥ 1, with i.i.d. increments, together with an arbitrary i.i.d. random scenery. Walk and scenery are assumed to be independent. Random walk in random scenery (RWRS) is the random process where time is indexed by ℤ, and at each unit of time both the step taken by the walk and the scenery value at the site that is visited are registered. Bad configurations for RWRS are the discontinuity points of the conditional probability distribution for the configuration at the origin of time given the configuration at all other times. We show that the set of bad configurations is non-empty. We give a complete description of this set and compute its probability under the random scenery measure. Depending on the type of random walk, this probability may be zero or positive. For simple symmetric random walk we get three different types of behavior depending on whether d = 1, 2, d = 3, 4 or d ≥ 5. Our classification is actually valid for a class of subshifts having a certain determinative property, which we call specifiable, of which RWRS is an example. We also consider bad configurations w.r.t. a finite time interval (replacing the origin) and obtain an almost complete generalization of our results. Remarkably, this extension turns out to be somewhat delicate.
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| 4. |
- Gururaj, AE, et al.
(author)
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MTA1, a transcriptional activator of breast cancer amplified sequence 3
- 2006
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:17, s. 6670-6675
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Journal article (peer-reviewed)abstract
- Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERa and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase 11 complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells.
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