Bioinformatics Lecture 1: molecular biology

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

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

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.

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

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)

Chromosome Mutations Adapted from ref [1] p. 121

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.

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

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.

Chromosome Mutations Adapted from ref [1] p. 121

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.

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

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).

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

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]

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.]

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