genetica - università degli studi di...
TRANSCRIPT
CORSO INTEGRATO DI GENETICA E BIOLOGIA MOLECOLARE
GENETICAA.A.2016/2017
prof. Giovanni Malerba [email protected]
Scansioni Genomiche II
- 75,891 inds of European ancestry (30 studies) - 67,786 i ndis of European ancestry from the UK Biobank; - 10,104 individuals: African American, Chinese, Filipino, Surinamese,Turkish and Moroccan (6 six studies)
IMPUTATION using 1000G + UK10K
60 loci (53 novel)
Associations between fetal genotype and BW could result from indirect effects of the maternal genotype influencing BW via the intrauterine environment, given the correlation (R ≈ 0.5) between maternal and fetal genotype. However, two lines of evidence indicatedthat variation in the fetal genome was the predominant driver of BW associations.
Hierarchical clustering of BW loci based on similarity of overlap with adult diseases, metabolic and anthropometric trait
Z scores
BMD e numero di alleli di rischio
La distribuzione del numero di alleli di rischio portati da un individuo si avvicina alla curva a campana
Il valore di BMD (espresso in Z-score), in media, si riduce all'aumentare del numero di alleli di rischio!! (ricorda il modello a soglia)
423 loci (697 variants) explain ~20% of the heritability~2000 SNPs → ~42% ~3700 SNPs → ~48%~9500 SNPs → ~58%
~253,000 individuals
Heritability of Height
FINRISK97 panel with complete genotype at the 12 SNPs with P <5 X 10-7 (7566 individuals),
Combined effects of 12 SNPs
~2% of the population variation in height
Difference : 3.5 cm
Combined impact of the 20 SNPs with a P < 5 x 10-7.
Combined effects of 20 SNPs
13,665 individuals(+ 16,482 samples)
~3% of height variation, with a ~5 cm difference
Autoimmune Disease Classification by Inverse Association with SNP Alleles
Marina Sirota Marc A. Schaub Serafim Batzoglou William H. Robinson Atul J. Butte
Disease heatmap based on genetic variation profile
● 8% of the general population carry a large deletion or duplication
(>500 kb) at low allele frequency of (<0.05%)● Several hundred genes that map to regions of copy-number
polymorphic (CNP) duplications● True associations are hidden in the fog of random associations● Interazioni di varianti in cis● Rare variants of large effect (?)● Gene–environment (G×E) interactions● Parent of origin effect (es. asthma, T2D)● Epigenome
Giovanni Malerba, [email protected] -
PROGETTO ENCODE
Slide 22/23
Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
Giovanni Malerba, [email protected] -
ENCODE – la variabilità
Slide 23/23
● TRANSCRIPTION FACTOR (TP) MOTIFS
● CHROMATIN PATTERNS AT TP BINDING SITES
● INTERGENIC REGIONS AND GENE DEFINITION
● RNA AND CHROMATIN MODIFICATION PATTERNS AROUND PROMOTERS
● EPIGENETIC REGULATION OF RNA PROCESSING
● NON-CODING RNA CHARACTERIZATION
● DNA METHYLATION
● ENHANCER DISCOVERY AND CHARACTERIZATION
● 3D CONNECTIONS ACROSS GENOME
● CHARACTERIZATION OF NETWORK TOPOLOGY
● MACHINE LEARNING APPROACHES TO GENOMICS
● IMPACT OF FUNCTIONAL INFORMATION ON UNDERSTANDING VARIATIONS
● IMPACT OF EVOLUTIONARY SELECTION ON FUNCTIONAL REGIONS