1. Bioinformatics Lecture 1: molecular biology

2. Background The student can refer to “overview of cell biology” look at the macroscopic manifestation of the ideas coved in the “biology” element of the course and so a more in depth “biological” explanation of terms used in the lecture: – What is a cell; – Different classification of organisms ; – Different cell States: mitosis, meiosis….. – Stages in multi-organism development

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 classified into 2 types chromosomal mutation and point mutations Diversity is determined by the cell type of the mutation – Somatic mutation: in the non reproductive cells; not passed on next generation – Germ-line mutation: reproductive cells [gametes] ; may passed on to next generation The Chromosome where the mutation occurs is important in determining the effect on the physical characteristics:[ refer to supplementary material on inheritance] Autosomal mutation (number 1 to 22) X-linked mutation X/Y chromosome

4. Chromosome Mutation: non-dysjunction. Non-dysjunction abnormality: – Dysjunction is an essential step in the process of meiosis (production of sexual productive cells) – 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 a non-disjunction while the other is normal has 1 (number 21) – The figure in the next slide shows the effect of the two possible areas for a non-disjunction abnormality to occur.

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

12. 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.

13. 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

14. 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).

15. 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

16. Supplementary material Supplementary material of this lecture refers to the idea(s) of inheritance of phenotypes [physical traits associated with a gene] and the different types of inheritance. It covers area such as: – How a traits are passed from parents to children: classical Mendelian inheritance – How it has a different implication for x-linked male mutations [e.g. haemophilia]

17. Possible Exam Describe, using suitable examples, three different types of chromosomal mutations at the DNA level [genotype] and what are the likely result of each type of mutations [would form part of a question] Describe the types of point mutations and how they would affect a DNA sequence. [would form part of a question.]

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