Transcript corso di Genomica 2010-2011 lezione 17-18

corso di Genomica 2010-2011
lezione 17-18
• laurea magistrale Biotecnologia
Industriale
Giovedì 9 dicembre 2010
aula 6
orario : Martedì ore 14.00 - 16.00
Giovedì ore 13.00 - 15.00
Lunedì 13 Dicembre seminario sequenziamento
c/o Fac.medicina ore 9.30 aula anfiteatro (p -1)
D. Frezza
In search of human variants
The 1000 genomes project
Rasmus Nielsen
2010 Nature vol 467 28 Oct.
News and views 1050-1051
applicazioni di HapMap
Once the information on tag SNPs from the HapMap is available,
researchers will be able to use them to locate genes involved in
medically important traits. Consider the researcher trying to find genetic
variants associated with high blood pressure. Instead of determining the
identity of all SNPs in a person's DNA, the researcher would genotype a
much smaller number of tag SNPs to determine the collection of
haplotypes present in each subject. The researcher could focus on
specific candidate genes that may be associated with a disease, or even
look across the entire genome to find chromosomal regions that may be
associated with a disease. If people with high blood pressure tend to
share a particular haplotype, variants contributing to the disease might
be somewhere within or near that haplotype.
1000 genomes project
Nature. 2010 Oct 28;467(7319):1061-73.
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project aims to provide a deep characterization of human genome
sequence variation as a foundation for investigating the relationship between genotype and
phenotype. Here we present results of the pilot phase of the project, designed to develop
and compare different strategies for genome-wide sequencing with high-throughput
platforms. We undertook three projects: low-coverage whole-genome sequencing of 179
individuals from four populations; high-coverage sequencing of two mother-father-child trios;
and exon-targeted sequencing of 697 individuals from seven populations. We describe the
location, allele frequency and local haplotype structure of approximately 15 million single
nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural
variants, most of which were previously undescribed. We show that, because we have
catalogued the vast majority of common variation, over 95% of the currently accessible
variants found in any individual are present in this data set. On average, each person is
found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50
to 100 variants previously implicated in inherited disorders. We demonstrate how these
results can be used to inform association and functional studies. From the two trios, we
directly estimate the rate of de novo germline base substitution mutations to be
approximately 10(-8) per base pair per generation. We explore the data with regard to
signatures of natural selection, and identify a marked reduction of genetic variation in the
neighbourhood of genes, due to selection at linked sites. These methods and public data
will support the next phase of human genetic research.
utilità ed uso dei 1000 genomes
in quale modo si applicherebbe la banca dati del
progetto dei 1000 genomi?
vedi articolo su Nature vol 467 del 28 Ottobre 2010
la prospettiva nel restante 95% del
genoma
genoma si ricomincia da capo
nell’interattoma va inserito il genoma e si
allargano le prospettive
nuove tecniche, metodi, strumenti
P.Fraser & W.Bickmore
Nature vol.447, 24 May 2007; 413-417
Nuclear organization of the genome and the potential for gene
regulation
lettura articolo news and views
“in search of human variants”
1000 genomes project
strategies, objectives, goals
discussion and work in progress
preliminary results
Rasmus Nielsen: Nature vol 467, 28 October 2010
pp 1050-1051