1. Bioinformatics Lecture 2: molecular biology

2. Essential concepts of evolution – The Basic Tenets of evolution: Adaptability and stability in an environment mutations/ survival of fittest – Basic Tenets of inheritance: How physical traits (phenotype) are transmitted at the genetic level (genotype) Different variants of the same gene (alleles) Relationship between alleles: dominant /recessive Two forms of inheritance,autosomal / x-linked, that are associated with the type of chromosome: non sex linked/sex linked (gender determination ) chromosomes

3. Stability and Adaptability Stability: cell/tissue remains in an unchanged state. Cell structure protects it from the external environment; nuclear membrane protects the DNA…. Adaptability: is essential to survival and creating the diversity of life that exists occur via mutations: A mutation is a change, mostly permanent, to the DNA and can be generalised into 2 forms: – Type: chromosomal “mutations” and point mutations – Cell location of mutation Somatic mutation: Diploid (2n) somatic cells Germ-line mutation: Haploid (n) reproductive cells [gametes] – Chromosome Location ( subset of cell location mutations): Autosomal (number 1 to 22): Huntington’s syndrome X-linked X/Y chromosome: Haemophilia

4. Chromosome Mutation: non-dysjunction. Non-dysjunction abnormality: – Cross-over is an integral part of meiosis and ensure greater diversity is passed from one generation to the next “parent to child” [refer to lecture 1] and an essential element is: dysjunction – However, non-dysjunction can lead to conditions such as Down’s syndrome; here one of the gamets reproduction cells) has 2 (number 21 chromsomes) due to non-disjunction [see next slide] while the other is normal has 1 (number 21)

5. Types of meiotic Non-dysjunction Adapted from [1] fig 6.1 p113

6. Chromosome mutations: deletion Deletion: – A chromosome breaks in one place or more places – The part that “falls off” the chromosome is lost – Most often fatal unless small portion lost (cri- du-chat syndrome: deletion in chromosome 5)

7. Chromosome Mutations Adapted from ref [1] p. 121

8. Chromosome mutations: duplication Duplication: – Due to error in cross- over or error in duplication prior to meiosis: – Can lead to “gene redundacy”, some physical “abnormality or even increase genetic variability.

9. Chromosome mutations: inversion Inversion: – No change to the amount of genetic material – A segment of the chromosome is turned around by 180 degrees – The physical consequences is minimal

10. Chromosome Mutations: translocation Translocation: Reciprocal and non reciprocal: – The movement of a chromosome segment to another part of the genome (between non-homologous chromosomes). – Genetic information is not lost or gained but only rearranged. – In reciprocal both chromosomes swap sections – In non reciprocal one loses a section and it is added to the other.

11. Point Mutations A Mutation affects only one DNA molecule – Can, but not always, change the type of amino acid [see later] – Substitution: Two types A /G is called a transition; T/C is called a transversion – Insertion : causes a frameshift to the left – the resulting sentence is non sense – Deletion : causes a frameshift to the right: the resulting sentence is non sense Note In genetics the bases (letter of a DNA molecule) are read in sets of three, where each 3 “can” have different result; just as in this example using 3 letter words).

12. Mutations: Physical (Phenotypic) effects Mutations “can” alter the current (wild type) protein [Phenotype] by changing the underlying Genotype Physical effects (phenotype) are: – Loss of function [can be fatal]: Null mutation (complete loss of function) Partial: can alter either dominant /recessive alleles ; so e.g. if it effects recessive then only homozygous recessive trait is affected – Gain in function: mostly produces a dominant trait – No affect: neutral mutations. Most mutations occur in non-coding regions and are referred to as

13. Inheritance If a gene has a two or more variants then these are called alleles; alleles are the result of mutations in gene. The presence of such alleles is the basis of differences between members of a species; Tall/dwarf [in certain plants]. Therefore each trait (phenotype/physical manifestation ) has two alleles associated with it. One on the chromosome from the male and one from the female; or one on each chromosome [in the chromosome pair]

14. Types of alleles-> Phenotype Dominant/recessive system – the dominant allele is capitalised/ recessive is lower case – In heterozygous only the dominant trait is seen. – In the homozygous it depends it can be either. Homozygous dominant: DD (Tall) Homozygous recessive: dd (dwarf ) Heterozygous: Dd (Tall) Incomplete / semi-dominance (snap dragon) – No allele dominant and mixed phenotype (red and white giving pink) Co-dominant (e.g. blood groups) – The phenotype of both alleles are equally expressed; AB, AA, BB, OO

15. Classical (autosomal) Mendelian Inheritance Somatic Monohybrid cross Adapted from ref [1] p42

16. Inheritance: Questions This is a dominant/recessive inheritance system. F1: stands for cross- pollination. What conclusion can you draw from F1 results? F2 is self pollination: How the ratios are obtained. For each example determine: – Which is the dominant/recessive trait. Adapted from ref [1] p. 39

17. X-linked inheritance Haemophilia: (a classical case is son Alexei of last tzar of Russia who was related to queen Victoria) – X chromosome has the normal/defective gene (H/h) – Y chromosome has no gene (smaller in size) – Defective allele is recessive – Male is XY and Female is XX – Homozygous defective results in the disease This includes a defective allele in males – Homozygous/heterozygous normal results in no physical effects.

18. Illustration of royal disease

19. Possible Exam Distinguish how x-linked/autosomatic mutations are transmitted throughout a population; illustrating you answer with suitable examples. Explain how mutations are essential for the adaptive character of living organisms and distinguish between the different types of mutations

20. Reference Klug et al; Essentials of Genetics 7ed – Chapter 6/ 14 (mutations) and Chapter 3 (inheritance)