Bioinformatics

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 typeschromosomal 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)