Lecture 2: The Human Genomes- From Reference to Reality

what does a human reference genome provide?

• coordinate system for studying genetic variation

• map for identifying genes and regulatory element

• foundation for disease genetics

• framework for functional genomics

• baseline for understanding human evolution

Human Genome Project: goal?

sequence the entire human genome

how many base pairs is the human genome, and how much did it cost

around 3 billion bp, cost 3 billion

what questions were raised regarding HGP

• who owns the human genome?

• should genomic data be patented?

what are some large-scale projects that followed(give 4)

• HapMap project

• UK Biobank

• 1000 Genomes Project

• ENCODE

today human genome focuses on?

population diversity, disease risk, functional interpretation

T2T-CHM13 reference

• first telomere to telomere human genome

• gapless assemblies of all chromosomes

• ~200 million bp of newly resolved sequence

• thousands of previously missing gene copies

Human Pangenome Reference Consortium

• graph based genome representation

• captures genomic diversity across populations(47 individuals)

• improves variant discovery and interpretation

human genome consist of?

• nuclear genome(~3.3 Gb)

• mitochondrial genome(~16.6kb)

• only ~1-2% encodes proteins

• majority is noncoding DNA

  • introns

  • regulatory regions

  • repetitive elements

• nearly half is repetitive DNA

nuclear genome

• linear DNA

• distributed across 23 chromosome pairs

• gene density is uneven

• biparental

• low density coding

• large

how do human genes vary

vary in length, number of exons, intron size

types of repetitive DNA

tandem and interspersed

tandem repeats

• repeats arranged next to each other

• found in centromeres and telomeres

• important for chromosome structure and stability

interspersed repeats- transposable elements

• DNA sequences that move or copy themselves

• mostly retrotransposons in humans

• use copy and paste mechanism

• still active today

importance of repeats

• shape genome architecture

• drive genome evolution

• influence gene regulation

• contribute to genetic variation and disease

mitochondrial genome

• circular DNA

• 37 genes

• very high coding density

• inherited maternally

what genes make up the 37 in mitochondrial genome

• 13 proteins, respiratory complex

• 22 tRNA

• 2 rRNA