Bioinformatics

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4 Οκτ 2013 (πριν από 3 χρόνια και 6 μήνες)

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Bioinformatics

Lecture 2: molecular biology

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




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




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)


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.



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


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]

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




Classical (
autosomal
)
Mendelian

Inheritance

Somatic Monohybrid cross Adapted from ref [1] p42

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

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.

Illustration of royal disease

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



Reference


Klug et al; Essentials of Genetics 7ed


Chapter 6/ 14 (mutations) and Chapter 3
(inheritance)