Genomes and Chromosomes

Genome and Chromosomes

• A genome is the entirety of genetic material (DNA) found within a cell or organism.
• DNA is made up of four nitrogenous bases: adenine (A), cytosine (C), guanine (G), and thymine (T).
• Chromosomes are linear elements that package DNA.

Karyotype

• A karyotype is the set of chromosomes found in a particular species.
• Mammals have a diploid karyotype, meaning they have two copies of each chromosome.
• Genome size and karyotype vary among mammals and do not relate to organism complexity.

Types of Chromosomes

• Autosomes are chromosomes that are diploid in all individuals of a species, regardless of sex.
• Sex chromosomes confer sexual traits and are different between males and females.
• In mammals, sex chromosomes are known as X and Y, and males are the heterogametic sex.

Chromosomal Structure

• Chromosomes have centromeres, which are the site of spindle attachment during mitosis.
• Chromosomes have telomeres, which are DNA sequences at the ends of chromosomes characterized by a conserved repeat structure.
• A chromosomal arm is the region from the centromere to the end of the telomere.
• The p-arm refers to the shorter of the two chromosome arms, and the q-arm to the longer arm.

Genome Composition

• The majority of the genome (~98%) is non-coding, meaning it does not encode protein-coding gene exons.
• The number of genes (~20,000) is fairly constant among mammals.

Reference Genome

• A reference genome is a completely sequenced genome isolate used as a reference for genetic studies.
• The human reference genome is the best assembled and annotated mammalian reference genome.
• Reference genomes exist for dozens of mammals, including dog, cat, and livestock species.
• Each base in the reference genome has its own unique genome coordinates, e.g., chr18:28,000,000, designating the 28,000,000th base on chromosome 18.

Indels

• Small insertions and deletions in DNA, usually defined as
• Involves insertion or deletion of a small number of nucleotides in a DNA sequence

Indels

• Small insertions and deletions in DNA, usually defined as
• Involves insertion or deletion of a small number of nucleotides in a DNA sequence

Transposable Elements

• Transposable elements are virus-like sequences that copy themselves and move around the genome.
• There are two types of transposable elements: autonomous and non-autonomous.
• Autonomous transposable elements, such as LINE elements, encode genes necessary for transposition, including reverse transcriptase.
• Non-autonomous transposable elements, such as SINE elements, rely on transposition proteins encoded by autonomous elements to support transposition.
• Transposable element insertions can disrupt genes and cause disease.
• An example of a disease caused by transposable element insertions is the merle phenotype observed in dogs.

Genome Variation Detection

• Genome variation is detected through whole genome sequencing.
• The process involves extracting DNA from cells and breaking it down into small, evenly-sized fragments.
• These fragments are then loaded onto a sequencing machine, which produces hundreds of millions of short sequences.
• Computer clusters (many computers working in parallel) are used to map these short sequence 'reads' back to the reference genome.
• Computational algorithms are used to identify variants, which are positions that differ between the sequenced genome and the reference genome.
• Whole genome sequencing can also identify copy number variants by detecting differences in the number of reads mapping to the reference genome.
• The current cost of sequencing a mammalian genome is approximately £1,000.