Human Genetics (one)

Why Study Genetics?

  • Genetics helps understand traits, behaviors, and disease susceptibility.

  • Access to genetic information has dramatically improved, with genome sequencing costing less than $500.

  • Genetic tests can determine the likelihood of expressing certain phenotypes, allowing for mitigation or preparation.

  • DNA is a biological blueprint that informs about traits and susceptibility to diseases.

Genetic and Environmental Contributions

  • Most traits have both genetic and environmental components.

  • Environmental exposures during life influence traits alongside genetic factors.

Definition of Genetics

  • Genetics is the study of genes, genomes, and inheritable variations.

Major Achievements in Genetics

  • Human Genome Project provided a template of over 3,000,000,000 bases.

Nuclear and Mitochondrial Genomes

  • Nuclear genome: 23 pairs of chromosomes with over 3,000,000,000 bases, inherited from both parents.

  • Mitochondrial genome: approximately 16,005 bases, maternally inherited.

DNA Packaging

  • DNA is tightly packaged into cells; if stretched out, it would be over a meter long.

  • DNA is packaged into nucleosomes, resembling beads on a string, with DNA wrapped around histone proteins.

  • Each nucleosome consists of eight histones.

Chromosomes

  • Humans have 22 chromosomes X and Y.

  • Chromosome size generally decreases from chromosome 1 to 22.

DNA Structure

  • DNA has a monomer structure, is anti-parallel, and forms a double-stranded helix.

  • It includes a sugar-phosphate backbone, minor and major grooves, and nitrogenous bases (A, C, T, G).

  • A always pairs with T, and C always pairs with G.

  • DNA strands run anti-parallel, with one strand going from 5' to 3' and the other from 3' to 5'.

Nucleotide Bases

  • Nucleotide base consists of a phosphate, sugar, and base (A, C, T, G).

  • Adenine and guanine are purines; cytosine and thymine are pyrimidines.

  • Purine-pyrimidine pairings (A-T, C-G) are crucial for DNA stability.

Transferring Genetic Information

  • Genetic information transfers from DNA to RNA to protein.

  • Transcriptional units called genes contain the information for this transfer.

Genome, Transcriptome, and Proteome

  • Genome (DNA) is transcribed into transcriptome (RNA species).

  • Transcriptome transfers information from the nucleus to the cytoplasm for translation.

  • Translation results in the proteome (proteins).

  • The transcriptome varies by cell type, reflecting cell-specific functions.

Gene Number and Similarities

  • Human genome contains around 22,000 genes.

  • Humans share many genes with other species.

  • Any two individuals share about 99.8% of their DNA.

Differences in DNA

  • Individuals differ by about 4,000,000 bases in their DNA.

Genes and Non-Coding DNA

  • Genes make up a portion of the genome; the rest is non-coding DNA.

  • Genes consist of introns and exons; exons contain coding information.

Gene Functions

  • Genes are involved in maintenance, replication, repair, and specific cellular functions.

  • Some genes are housekeeping genes, essential for cell survival.

  • Others are associated with specific functions or immune response.

Genes Examples

  • Examples include the sex-determining gene, hemoglobin gene, and TP53 gene.

  • Gene sizes vary significantly, with the dystrophin gene being one of the largest.

Transcription Overview

  • Genetic information transfers via transcription (DNA to RNA) and translation (RNA to protein).

  • Transcription involves RNA intermediate called messenger RNA (mRNA).

  • Primary transcript includes both intron and exon structure; introns are spliced out.

Transcription Process

  • RNA polymerase forms a complex with DNA at the promoter region.

  • Transcription factors facilitate this process.

RNA Polymerase

  • RNA polymerase synthesizes a new RNA strand in the 5' to 3' direction.

  • It uses the template strand (antisense) to create a complementary RNA sequence.

  • RNA includes uracil (U) instead of thymine (T).

RNA vs DNA

  • RNA is typically single-stranded and contains ribose instead of deoxyribose.

Gene Structure

  • Genes include promoter regions, exon-intron structure, and termination signals.

  • RNA polymerase adds a poly-A tail and a five prime cap for stability and trafficking.

Splicing

  • Introns are spliced out to produce a mature RNA transcript.

Alternative Splicing

  • Alternative splicing can produce multiple proteins from a single gene by selectively using or skipping exons.

Regulation of Transcription

  • Regulation involves regulatory elements, non-coding RNA, and epigenetics.

  • Enhancers regulate gene expression in response to the environment.

MicroRNAs

  • MicroRNAs are non-coding RNAs that bind to complementary regions on DNA.

  • They can signal transcript degradation, regulating transcription levels.

Epigenetics

  • Epigenetics involves chemical modifications to histone proteins, affecting DNA packaging.

  • Modifications like methyl or acetyl groups can open or close DNA structure.

Histone Tails

  • Chemical moieties on histone tails modify DNA packaging affecting transcription accessibility.

Cancer and Epigenetics

  • Alterations to epigenetic tags can cause aberrant gene expression in cancer.