DNA, Chromosomes & Human Genome

DNA, Chromosomes & Human Genome

• Genetics is the study of the origin, transmission, and expression of genetic information.
• Medical Genetics is the branch of medicine focusing on inheritance, diagnosis, and treatment of genetically-based diseases.
• Molecular Genetics studies the structure and function of genes at a molecular level.
• Cytogenetics studies chromosomes, their structure, and inheritance.

What is the Genetic Material?

• The genetic material is DNA.
• DNA is arranged in structures called chromosomes.

DNA

• DNA is a double helix composed of nucleotides.
• Nucleotides have a phosphate group, a sugar, and a nitrogenous base.
• The sugar in DNA is deoxyribose.
• The nitrogenous bases are adenine (A), thymine (T), guanine (G), and cytosine (C).
• A pairs with T, and G pairs with C.
• The strands are anti-parallel.
• DNA is usually found in the nucleus of eukaryotic cells.
• DNA in a cell is referred to as the genome.

DNA Packaging

• DNA is associated with proteins (histones), coiled to form chromatin.
• The fundamental unit of chromatin is the nucleosome.
• Nucleosomes consist of DNA wrapped around a core of histone proteins.
• DNA forms a filament (11nm).
• The nucleosome filament coils into a solenoid (~30nm).
• Loops of chromatin fibers bind to non-histone proteins to form looped domains (~70nm).
• Looped domains further compact to form the chromatid.
• The final compact form of DNA is the chromosome (1400nm).

Chromosomes

• Chromosomes are rod-shaped structures found in the nucleus.
• Each chromosome is composed of one double-stranded DNA molecule and protein.
• Humans have 46 chromosomes in somatic cells.
• The first 22 pairs of chromosomes (autosomes) are identical in both sexes.
• The 23rd pair is the sex chromosome; they differ between sexes (XX in females, XY in males).
• Gametes (sperm and ova) have 23 chromosomes.

General Organization of Human Genome

• The human genome is the complete set of genes in a human cell.
• Human genome contains approximately 20,000–40,000 genes in the nuclear genome.
• Nuclear DNA makes up 99% of the human genome and is passed on from both parents.
• Mitochondrial DNA (mtDNA) makes up 1% of the genome. The mtDNA is inherited solely from the mother.
• mtDNA is circular and contains only 37 genes.

Nuclear Genome

• Nuclear genome is linear double-stranded DNA.
• It occupies 3.1 Gb (~3.1 billion base pairs).
• Distributed amongst 46 chromosomes (44 autosomes, 2 sex chromosomes).
• Genes vary in distribution among chromosomes, some are gene dense chromosomes (e.g., 19 & 22), and some are gene poor (e.g., 4 & 18).
• The Nuclear genome contains single-copy DNA (unique DNA) and repetitive DNA sequences.

Repetitive DNA Sequences

• Repetitive DNA includes tandem repeats (e.g., satellite DNA) and dispersed repeats (e.g., SINES and LINES).
• Tandem repeats are short nucleotide sequences repeated in tandem.
• Dispersed repeats are scattered throughout the genome.

Mitochondrial Genome

• Mitochondrial DNA is circular, double-stranded DNA found in mitochondria.
• It is ~16kb (~16 thousand base pairs) in size.
• Inherited only from the mother.
• Contains 37 genes that encode proteins essential for energy production in the mitochondria.