human genome project

human genetics lecture 12

haemophilus influenzae

first organism to have its entire genome sequenced, gram-negative bacteria, responsible for several infections like meningitis

goals of the human genome project

• sequence all of the euchromatic DNA in the human genome

• identify and map the thousands of genes to the 24 human chromosomes

• assign a function to all the genes in the human genome

shotgun sequencing

• generate minimally-overlapping DNA clones in bacterial vectors

• amplify those clones via PCR with labelled nucleotides

• sequence those clones using gel electrophoresis

• map onto chromosome regions using FISH

• assemble the myriad clones into a contiguous sequence

key dates of the human genome project

• 1990: project began

• 2003: sequenced all protein-coding genes

• 2006: sequenced all chromosomes

• 2009: Genome Reference Consortium released a more accurate version of the human genome with fewer gaps

• 2020/2021: telomere-to-telomere sequencing of the X chromosome completed (including heterochromatic DNA)

then vs. now comparison of the human genome project

• cost: decreased exponentially

• time: decreased to a matter of weeks / months

genome annotation

analysis of genomic nucleotide sequence data to identify protein-coding genes, non-protein-coding genes, their regulatory sequences and functions

open reading frame

includes the codons in a gene that encode the amino acids of the gene product (exons), along with all possible splice variants

discoveries from the human genome project

• only about 2% of the human genome encodes protein information

• humans have approximately 22 300 genes

• genes are distributed unequally on chromosomes

• there are more proteins than genes in the body

• genomes of humans and other higher organisms are similar

• new disease-related types of mutation have been discovered

  • different mutations in a single gene can give rise to different genetic disorders

• nucleotide variation is common

emerging fields from the human genome project

• bioinformatics

• genomics

bioinformatics

the use of software, computational tools, and databases (nucleic acid and protein information) to acquire, store, analyze, and visualize the information from genomics

genomics

the study of the organization, function, and evolution of genomes

goals of genomics

• create genetic and physical maps of genomes

• find locations of all genes in a genome and annotate each gene

• compile lists of expressed genes and non-expressed sequences

• elucidate gene function and gene regulation

• identify all proteins encoded by a genome and their functions

• compare genes/proteins between species

• characterize DNA variations within and between genomes

• implement and manage web-based databases

sub-fields of genomics

• comparative genomics

• structural genomes

• pharmacogenomics

comparative genomics

compares genomes of different species for clues to the evolutionary history of genes or a species

structural genomics

derives three-dimensional structures for proteins

pharmacogenomics

analyzes genes and proteins to identify targets for therapeutic drugs

proteomics

the study of the structure, function, and expression of proteins, which is important in development of new diagnostic tests and drugs

role of proteomics

• understanding gene function and its changing role in development and aging

• identifying proteins that are biomarkers for diseases → used to develop diagnostic tests

• finding proteins for development of drugs to treat diseases and genetic disorder

protein signature

proteins are labelled and separated along two dimensions

• isoelectric point

• molecular mass

isoelectric point

pH at which the molecule has a net neutral charge

fields targeted for development as genomic and genetic information grows

• resources → genome sequence and libraries

• technology → new sequencing methods

• software for computational biology

• training professionals in interdisciplinary skills

• ethical, legal, and social implications

• education of health professionals and public