Friday Facts, September 26, 2014, Vol. 225

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, October 3, 2014, Vol. 226

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, October 10, 2014, Vol. 227

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, October 17, 2014, Vol. 228

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, October 24, 2014, Vol. 230

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Copy number variation modifies expression profiles over developmental time

Abstract : A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were shown to influence, in a somewhat dose-dependent manner, the expression of genes mapping within them. They were also shown to modify the expression of genes located on their Hanks, sometimes at great distance. Here, we demonstrate by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained through life. However, 'we find that some brain- expressed genes mapping within CNVS appear to be under compensatory loops only at specific time-points, indicating that the effect of CNVS on these genes is modulated during development. Notably, we also observe that CNV genes are significantly enriched within transcripts that show variable time-course expression between strains. Thus, modifying the copy number of a gene may potentially alter not only its expression level, but its timing of expression as well. Résume : Nous commençons à comprendre les effets phénotypiques liés aux séquences d'ADN qui changent de nombre de copies d'un individu a l'autre. Des travaux précédents ont montré que ces variante de nombre de copies (CNVS) avaient une influence sur l'expression non seulement des gènes se trouvant dans le réarrangement, mais aussi sur ceux se trouvant à une certaine distance. Le présent travail étudie ces effets à différents stades du développement de la souris allant d'un embryon de deux semaines à la souris adulte. Nous avons observé que certains gènes exprimés dans le cerveau semblent soumis à un contrôle plus strict a certaines étapes du développement suggèrent que l'effet des CNVs est modulé différemment au cours de la vie. Notre travail sur trois souches différentes de souris a permis de montrer que les gènes ayant un profil d'expression différent dans le temps entre souches sont enrichis en gènes se trouvant dans des CNVs. Ceci nous amène à penser que les CNVs ont, non seulement une influence sur le niveau d'expression des gènes, mais aussi sur les moments durant lesquels ils seront exprimés. Résumé pour un large public : De nombreuses maladies sont dues soit a un gain (on parle alors de duplication) soit à une perte de matériel génétique (il s'agit dune délétion). Bien que les recherches visant à identifier les mécanismes moléculaires liés à ces réarrangements de notre génome progressent continuellement, la plupart des causes des maladies génétiques restent à élucider. Certaines parties de notre génome sont présentes en un nombre de copies qui diffère d'un individu à l'autre sans pour autant provoquer une ou des maladies. Ces segments d'ADN qui varient en nombre sont appelés Copy Number Variant (CNVs). Ils couvrent environ 12% de notre matériel génétique. Des études menées sur différents modèles animaux ont montré que les CNVs avaient une influence aussi bien sur les gènes qui sont a l'intérieur des CNVs que sur ceux qui sont dans leur voisinage. Ce travail étudie l'effet des CNVs à travers différents stades du développement de la souris. Nous avons démontré que les segments d'ADN qui varient en nombre de copies ont des effets variables selon le stade auxquels ils sont mesurés. Ainsi, les CNVs ont non seulement un impact sur l'expression des gènes présents dans ces régions et dans leur voisinage, mais influencent également leurs profils d'expression au cours du temps.

Friday Facts, October 31, 2014, Vol. 231

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, October 31, 2014, Vol. 231

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, November 7, 2014, Vol. 232

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, November 14, 2014, Vol. 233

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant.

Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.

Friday Facts, November 21, 2014, Vol. 234

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, December 5, 2014, Vol. 235

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, December 12, 2014, Vol. 236

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.