Topic 1 - The Architecture of Human Genome (Moodle) Fill-In

The Architecture of Human Genome

• The human genome comprises nuclear DNA and mitochondrial DNA (mtDNA).

• The Human Genome Project (HGP) aimed to map all genes of human beings and further understand the structure and functions of the human genome.

Lesson Plan Overview

Flow of Genetic Information

• Topics:

  • Mitochondrial DNA (mtDNA)

  • Nuclear DNA

  • Human Genome Project (HGP)

  • Repetitive DNA sequences

  • Organization of nuclear DNA

Cell Division and Chromosomal Structure

• Mitosis (somatic cell division)

• Meiosis (germ cell division)

• Karyotyping

Objectives of This Lecture

• Distinguish between mtDNA and nuclear DNA.

• Describe levels of DNA packaging and organization.

• Identify key chromosomal components.

• Explain processes of mitosis and meiosis.

• Determine chromosome and chromatid numbers before and after cell divisions.

• Define key terms: nucleosome, chromatin, chromatid, chromosome.

DNA Structure and Flow of Genetic Information

• The flow of genetic information follows:

  • DNA → RNA (transcription) → Protein (translation)

• Directionality:

  • DNA strand: 5’ to 3’

  • RNA translation: Met, Ser, Ala, Leu, Val

Overview of Human Chromosomes

• Humans have 46 chromosomes, arranged in 23 pairs:

  • 22 pairs of autosomes (ranked by size)

  • 1 pair of sex chromosomes: XX (female) and XY (male)

Mitochondrial DNA (mtDNA)

• Mitochondrial DNA is circular, lacks introns, and is exclusively maternally inherited.

• Size: 16.5 kb encodes 37 genes:

  • 2 rRNAs

  • 22 tRNAs

  • 13 proteins for mitochondrial oxidative phosphorylation.

Organization of Human Mitochondrial Genome

• Mitochondrial DNA consists of heavy (H) and light (L) strands.

• Contains a unique D-loop (displacement loop) with a control region and replication variability.

Mitochondrial Genetic Code

• Mitochondrial genetic code is non-universal.

• While most mitochondrial proteins (> 99%) are encoded by nuclear genome, mitochondrial rRNAs and tRNAs are transcribed from mtDNA.

Packaging of mtDNA

• The compact mtDNA utilizes overlapping coding sequences and minimum spacers to maximize the use of its limited nucleotide space.

Maternally Inherited Diabetes and Deafness (MIDD)

• Affects 1% of diabetic patients, particularly in the Japanese population, caused by mutations in mitochondrial genes that reduce tRNA activities.

Nuclear (Chromosomal) DNA

• The nuclear genome consists of approximately 3.1 Gb of DNA (haploid). Less than 1.5% encodes proteins (~20,000 protein-coding genes).

• About 50% is unique, the remainder being repetitive DNA.

Human Genome Project Findings

• Comparison data from GRCh38.p12 (November 2017) for:

  • Total genes and pseudogenes: 54,274 (NCBI), 58,381 (GENCODE)

  • Protein-coding transcripts: 20,070 (NCBI), 113,224 (GENCODE)

  • Noncoding RNA transcripts and pseudogenes also show variability in counts.

Transcription Complexity

• Read-through transcription allows some genes to produce both protein-coding mRNAs and functional noncoding RNA transcripts. Example: 500 human cases identified.

Protein Systems and Export

• Functional RNAs are varied; essential processes include:

  • Splicing

  • RNA maturation

  • Gene regulation

  • Transposon control

  • RNAi-based gene silencing

Polymorphism and Reference Gene Sequence

• Comparison of the double helix reference sequence across individuals highlights polymorphisms.

Repetitive DNA Sequences Classification

• Clustered tandem repeats (satellite DNAs): constitute 10-15% of the genome, act as molecular markers.

• Dispersed repetitive DNA families:

  • Alu family: > 10% of the genome.

  • LINE (L1) family: ~20% of the genome.

Levels of DNA Packaging into Chromosomes

• Consists of condensed mitotic chromosomes through structures such as:

  • Nucleosomes (10 nm)

  • Histones

Cell Division: Mitosis and Meiosis

• Mitosis involves sepation of sister chromatids, while meiosis results in gamete formation, reducing the chromosome number by half.

Chromosome Structure in Human Karyotype

• Includes:

• Telomeres, centromeres, and arms (q and p).

Ploidy and Chromosome Number

• Diploid: 2n (two copies of each chromosome); haploid: n (one copy).

• Chromatid counting (c) post-DNA replication indicates chromosomal organization before and after cell division.

Meiosis and Genetic Variation

• Nondisjunction leads to abnormal chromosome distributions during meiosis.

Conclusion and Summary

• Genetic information is encoded within both mtDNA and nuclear DNA.

• Understanding chromosome organization is crucial for studying genetic disorders and for advances in genetics.