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 (cridu-chat syndrome:
deletion in chromosome
5)
Chromosome Mutations
Adapted from ref [1] p. 121
Chromosome mutations: duplication
• Duplication:
– Due to error in crossover 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 crossover 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)