THE HUMAN GENOME

Sachin S Rawat04716001311

THE HGP Took $3 billion and 15 years to complete. Race between DOE-NIH (hierarchical shotgun) and Celera Genomics (whole genome shotgun). Sequenced only euchromatic regions (~90% of the genome). >92% of sampling exceeded 99.99% accuracy.

Hierarchical shotgun sequencing Whole genome shotgun sequencing

THE HUMAN GENOME GRCh38 – Annotation Release 106 23 pairs of chromosomes amounting to 3.23gb. Chromosomes range in size from 48mb (21) to 249mb (1). 29,399 genes – 68.9% code for proteins, <2% of the genome. 2.93 transcripts per gene, 11.4 exons per transcript. High gene density in chromosomes 19, 11, and 1. Gene size varies from 781nt (H1a) to 2.2mb (dystrophin). Repetitive DNA sequences make up 50% of the genome.

Source: Mikael Häggström; Medical gallery of Mikael 

ENCyclopedia Of DNA Elements 80.4% of human genome now associated with biochemical functions. 95% of genome lies within 8kb of a DNA-protein interaction. 90% SNPs found in non-coding regions. 399,124 regions serve as enhancers and 70,292 as promoters. Promoter functionality correlates with RNA expression variation. Long-range chromatin interactions facilitated by looping.

Elements Techniques

Observations

RNA RNA-seq,

CAGE, RNA-PET

10-12 expressed isoforms per gene per cell line. 6% of transcripts overlap with sRNAs. Range of expression spans 5-6 orders of magnitude.

Protein-bound

ChIP-seq 636,336 binding regions cover 8.1 % of the genome.

DNase I hyper-sensitive sites

Dnase-seq,

FAIRE-seq

Aggregate to 3.9% of the genome. Average of 1% of the genomic sequence in a cell type.

DNA methylation

RRBS 96% CpGs show differential methylation. Variable methylation seen more in (inter)genic regions.

Long-range interactions

3C, 5C,ChIA-PET

Average of 3.9 distal elements interact with each TSS. Average of 2.5 TSSs interact with a distal element.

MITOCHONDRIAL GENOME Double-stranded, circular molecule of 16,569bp. Contains 37 genes coding for two rRNAs, 22 tRNAs, and 13 polypeptides. Code for subunits of enzyme complexes of the oxidative phosphorylation system. Replication controlled by nuclear genes, mtDNA has three promoters (H1, H2, and L). Transcription involves POLRMT, TFAM, TFBIM, and TFB2M. Paternal mtDNA inheritance in humans? Correlation between heteroplasmy and mitochondrial diseases?

World map of human migrations

APPLICATIONS Forensics Studying human evolution Personalized genomics and medicine Family genome sequencing

REFERENCES The ENCODE project consortium; An integrated encyclopedia of DNA elements in the human genome; Nature (2012) Anderson et al.; Sequence and organization of the human mitochondrial genome; Nature (1981)