* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Human Genome Project
Genomic imprinting wikipedia , lookup
Segmental Duplication on the Human Y Chromosome wikipedia , lookup
Comparative genomic hybridization wikipedia , lookup
Genealogical DNA test wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Gene desert wikipedia , lookup
Molecular cloning wikipedia , lookup
Short interspersed nuclear elements (SINEs) wikipedia , lookup
Primary transcript wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Cancer epigenetics wikipedia , lookup
DNA sequencing wikipedia , lookup
Zinc finger nuclease wikipedia , lookup
Epigenomics wikipedia , lookup
Copy-number variation wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
Gene expression profiling wikipedia , lookup
Mitochondrial DNA wikipedia , lookup
Human genetic variation wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Bisulfite sequencing wikipedia , lookup
Extrachromosomal DNA wikipedia , lookup
Deoxyribozyme wikipedia , lookup
Point mutation wikipedia , lookup
Genetic engineering wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Public health genomics wikipedia , lookup
Transposable element wikipedia , lookup
Oncogenomics wikipedia , lookup
Genome (book) wikipedia , lookup
Microsatellite wikipedia , lookup
Microevolution wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Designer baby wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Pathogenomics wikipedia , lookup
Minimal genome wikipedia , lookup
Metagenomics wikipedia , lookup
Non-coding DNA wikipedia , lookup
History of genetic engineering wikipedia , lookup
Whole genome sequencing wikipedia , lookup
Human genome wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Helitron (biology) wikipedia , lookup
Genomic library wikipedia , lookup
Genome editing wikipedia , lookup
Human Genome Project wikipedia , lookup
Human Genome Project • • • • Seminal achievement. Scientific milestone. Scientific implications. Social implications. HGP: Background • International Human Genome Sequencing Consortium: Proposed 1985, endorsed in 1988. 20 governmental groups. “Public project.” Craig Venter & Celera Genomics: Founded 1998. Sequence in 3 years. Technology: automation, computers. Had access to public project’s data. Race ends in tie Feb. 2001: both publish in Science and Nature. International Human Genome Sequencing Consortium • Approach was conservative and methodical. • Had to wait for technology. • First produced a clone-based physical map of the genome that would serve as a scaffold for the later sequence data: – Broke genome into chunks of DNA whose position on chromosome was known from maps, clone into bacteria using BACs. – Digest BAC-inserted clonal chunks of DNA into small fragments. – Sequence small fragments. – Stitch together BAC clones to assemble sequence. – Assemble genome sequence from BAC clone sequences, using clone-based physical map. Celera • Approach using "shotgun sequencing" (no organized map). • Shreds genome randomly into small fragments with no idea of where they are physically located. • Clones and sequences fragments. • Uses computer to stitch together genome by matching overlapping ends of sequenced fragments. Timeline • Genome sequencing driven by technology. – 1985: 500 base pairs per day by hand. – 1985-86: PCR and automated DNA sequencing. – 1992: BACs. – 2000: 1000 bases per second. Waiting for Technology • Eyes on the human genome. • While waiting for technology other genomes were sequenced. Current Status • Human genome ~3.2 Gb. • “Rough draft” sequence of the human genome. • Have sequenced 90% of the 2.5 Gb of generich (euchromatic) DNA. • What is considered finished? – Fewer than 1 base in 10,000 is incorrectly assigned. – More than 95% of the euchromatic regions are assigned. – Each gap is smaller than 150 kb. Access to Information • All public project data on the Internet. • NCBI Website: www.ncbi.nlm.nih.gov. – Human genome database. – Sequence and mapping tools. Database Search Example • The genome database has many tools to locate a gene of interest or search for potential traits of the gene. • Example–chromosomal map search result for the "breast cancer–causing gene" BRCA2: Early Statistics • Only 28% is transcribed into RNA. • Only 1.1%-1.4% of genome actually encodes protein (=5% of transcribed RNA). • Surprises: – More junk DNA. – Fewer genes. Junk DNA • • • • No apparent direct biological function. Long stretches of repeated sequence. Hot area of investigation. Human genome has far more repeat DNA than any other sequenced organism (over half). • Parasitic elements–45% of this repeat DNA is from selfish, parasitic DNA: – Transposable elements. – May play role in evolution. Gene Count • Many fewer genes than expected (half): – Only 35,000-45,000 genes vs. previously predicted 100,000. – Only twice the amount of a nematode or a fruit fly. – Does not correlate to twice as complex. – Alternative splicing: Invertebrate genes are more innovative in their assembly of genes. – Protein domains are mixed more creatively and in larger numbers by invertebrates. • Genes elusive. Genetic Variation • The International Single Nucleotide Polymorphism (SNP) Map. – Compiled 1.4 million SNPs (single-base pair differences between individuals). • Investigate: – – – – – Disease resistance. Response to therapeutics. Evolution. Natural selection. Individual traits. Gene Variation Example • Mutations in "breast cancer gene” BRCA2. • Chromosomal location and beginning sequence with one of the mapped variations. Future Directions • Fill gaps (refinement). • Bioinformatics. • Sequence additional genomes. – For comparison. – Upcoming: mouse, fish, dogs, kangaroo, chimpanzee (most valuable). • Proteomics. • Gene and Protein Chips (Microarrays).