Lec10 Mutation

8/13/2019 Lec10 Mutation

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Contents

Chromosomal changes and gene mutations: types of

chromosomal mutations, variation in chromosomal

structure ,variation in chromosomal number ,

chromosomal rearrangements consequences of

mutations, occurrence and causes of mutations



Mutations



What Are Mutations?

Changes in the nucleotide sequence

of DNA

May occur in somatic cells (aren’t

passed to offspring)

May occur in gametes (eggs &

sperm) and be passed to offspring



Are Mutations Helpful or

Harmful?

Mutations happen regularly

Almost all mutations are neutral

Chemicals & UV radiation cause mutations

Many mutations are repaired by enzymes

Some type of skin cancers and leukemia result from

somatic mutations

Some mutations may improve an organism’s survival (beneficial)



Types of Mutations

I. Chromosomal mutation

II. Gene mutation



Deviations from an organism’s normal

number of chromosomes, or their

structure, are called chromosomal

mutations or chromosomal

aberrations

I.Chromosomal mutation



Chromosomal mutations may be divided

into two broad categories:

1. Structural changes - Involves Change

in the structure of chromosome

2. Numerical change -Involves Change

in the number of chromosomeof

chromosome



1.Structural changes

Mutations involving changes in chromosome structure

are of four types

a) Deletions

b) Duplications

c) Inversions

d) Translocations



DeletionDeletions involve the loss of a chromosome segment

Because these mutations are due to the loss of genetic

material, they cannot revert to wild type.

The effects of the deletion depend on which genes are

deleted



Effect of delition in human

1)Cri Du Chat(CDC) – genetic disorder due to

deletion of part of the short arm of

chromosome 5.

1/50,000 births

Crying babies sound like cats;

mental disability Death by about 4years.

2)Wolf-Hirschhorn syndrome – delition of

short arm of chromosome 4

3)Philadelphia syndrome- delition of long

arm of chromosome 22.



A segment of chromosome is doubled

Types:

(i) Tandem duplication – ABC*DEFGH ABC*DEFDEFGH

(ii) Reverse duplication – ABC*DEFGH ABC*DEFFEDGH

(iii) Displaced duplication – ABC*DEFGH ABC*DEFGHDEF

A good example of duplication is seen in the Bar mutants of Drosophila

Duplication



Fig.:- Drosophila Bar and double-Bar results from duplications caused by unequal

crossing-over (Bridges & Müller 1930s).



Translocation

• Involves two chromosomes that aren’t

homologous

• Part of one chromosome is transferred to

another chromosomes



Types

• Intrachomosomal

• Interchromosomal

•

Reciprocal - segments are exchanged.• Non-reciprocal - no two-way exchange.

• Several human tumors are associated with chromosome

translocations; myelogenous leukemia (OMIM-151410) and

Burkitt lymphoma (OMIM-113970).



Inversion

An inversion results when a segment of a chromosome gets

reoriented 180

o

from normal

This requires two breaks in the chromosome



Numerical aberration in chromosome

1.Aneuploidy 2.Euploidy

Aneuploidy = variation in the number of individual chromosomes (but not

the total number of sets of chromosomes).

Nondisjunction during meiosis I or II aneuploidy.



Types of Aneuploidy:

1)Nullisomy = loss of one homologous

chromosome pair.(2n-2)

2) Monosomy = loss of a single

chromosome.(2n-1)

3) Trisomy = one extra chromosome.(2n+1)

4) Tetrasomy = one extra chromosome pair.(2n+2)

5) Double trisomy=extra copy of two

different non homologous chromosome.

(2n+1+1)

6) Double monosomy=two fewer non

homologous chromosome.(2n-1-1)

7) Double tetrasomy=two extra pair of

homologous chromosome.(2n+2+2)



Euploidy- Change in no. of whole

chromosome set

Monopioid(x)= No of chromosomes in

basic set

Euploidy= multiples of basic

chromosome set.

Haploid- 1 chromosome sets

Diploid- 2 chromosome set

Aberrant euploid: more or less than the

normal number.

- monoploid(1x)

- triploid (3x)

- tetraploid (4x)

- pentaploid (5x)

- hexaploid (6x)



Aneuploid abnormalities in human population:

Trisomy-13 - Patau Syndrome 2/10,000 live

births

Characteristics include i. Cleft lip and palate.

ii. Small eyes.

iii. Polydactyl (extra fingers and toes).

iv. Mental and developmental retardation.

v. Cardiac and other abnormalities



Trisomy-18 - Edwards Syndrome 2.5/10,000 live births

Characteristics include

i. Small size with multiple congenital malformations throughout

the body.

ii. Clenched fists.

iii. Elongated skull.

iv. Low-set ears.

v. Mental and developmental retardation



Trisomy-21 - Downs Syndrome 14.3 / 10,000 live birth

Down syndrome individuals are characterized by:

(1) Low IQ.

(2) Epicanthal folds over eyes.

(3) Short and broad hands.

(4) Below-average height.



Sex Chromosome Abnormalities

Klinefelter’s Syndrome

XXY, XXYY, XXXY Male

Sterility

Small testicles

Breast enlarges



Turner Syndrome - 1 / 5000 live births

• XO

•females •Short stature (143-145cm tall)•Loss of ovarian function•Hormone imbalances( thyroid,diabetes)•Stress and emotional deprivation

•Diseases affecting the kidneys, heart,lungs or intestines• Learning problems( esp. in maths)



Cystic Fibrosis (CF)

Monogenic

Cause: deletion of only 3 bases on chromosome

7

Fluid in lungs, potential respiratory failure

Common among Caucasians…1 in 20 are

carriers

Therefore is it dominant or recessive?



Tay-Sachs disease

Monogenic, autosomal recessive

Central nervous system degrades, ultimately

causing death.

Most common among people of Jewish, eastern

Europe descent.



Muscular Dystrophy

What Is Muscular Dystrophy? Muscular dystrophy is a disease in which

the muscles of the body get weaker and

weaker and slowly stop working because of a

lack of a certain protein

Can be passed on by one or both parents,

depending on the form of MD (therefore is

autosomal dominant and recessive)



Hemophilia, the royal disease Hemophilia is the oldest

known hereditarybleeding disorder.

Caused by a recessivegene on the Xchromosome.

There are about 20,000hemophilia patients inthe United States.

One can bleed todeath with small cuts.

The severity ofhemophilia is related tothe amount of theclotting factor in theblood.

About 70% ofhemophilia patientshave less than onepercent of the normalamount and, thus, havesevere hemophilia.



Huntington’s Disease

Huntington's disease

(HD) is an inherited,degenerative brain

disorder which results

in an eventual loss of

both mental andphysical control.

The disease is also

known as Huntington's

chorea. Chorea means"dance-like

movements" and

refers to the

uncontrolled motions

often associated with



Huntington’s

Looking back at the pedigreechart is Huntington’sdominant or recessive?

Scientists have discoveredthat the abnormal proteinproduced by the Huntington'sdisease gene, which containsan elongated stretch of amino

acids called glutamines,binds more tightly to HAP-1than the normal protein does.



Color Blindness

Cause: x-linkedrecessive

1/10 males have,1/100 females have.Why the difference?

Individuals areunable to distinguishshades of red-green.



Are you color blind

http://images.google.com/imgres?imgurl=www.richmondproducts.com/images/4420Rpg5colorblindnesschart.jpg&imgrefurl=http://www.richmondproducts.com/Color%20Blindness%20Quick.htm&h=433&w=574&prev=/images?q=color+blindness+chart&svnum=10&hl=en&lr=&ie=UTF-8&oe=UTF-8&sa=G



Albinism Patients are unable to produce skin or eye

pigments, and thus are light-sensitive

Autosomal recessive

Therefore, it is chromosomal disorder

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http://images.google.com/imgres?imgurl=http://www.npaphoto.com/webgallery/WebPortfolio4-03/images/Albinism.jpg&imgrefurl=http://www.npaphoto.com/webgallery/WebPortfolio4-03/pages/Albinism.htm&h=420&w=326&sz=55&tbnid=A9OEZTTdGVoJ:&tbnh=121&tbnw=94&start=21&prev=/images?q=albinism&start=20&hl=en&lr=&safe=active&sa=N

http://images.google.com/imgres?imgurl=http://www.mrcophth.com/iriscases/albino11.JPG&imgrefurl=http://129.195.254.71/cgi-bin/HONmedia?image+C16.131.410.040.100&h=287&w=471&sz=16&tbnid=FWzzmasNzv0J:&tbnh=76&tbnw=125&start=2&prev=/images?q=albinism&hl=en&lr=&safe=active&sa=N



There are two main categories of albinism in humans.

oculocutaneous albinism:-Pigment is lacking inthe eyes, skin and hair.

ocular albinism:-Only the eyes lack pigment.

Signs and symptoms

Lack of pigment in the eyes also results in problemswith vision, related and unrelated to photosensitivity.

Skin can burn more easily from overexposure of

Ultraviolet radiations because melanin absent which

protect in normal case.



II. Gene Mutations

Change in the nucleotide sequence of a

gene

May only involve a single nucleotide May be due to copying errors, chemicals,

viruses, etc.



o n



o nMutation

Change of a single nucleotide. Includes the deletion, insertion, or substitution of

ONE nucleotide in a gene.

Sickle Cell disease is the result of one nucleotide

substitution

Occurs in the hemoglobin gene

S b tit ti t ti h b i



Substitution mutation - when a base is

replaced with a different base.

CGG CCC AAT to CGG CGC AAT

Guanine for Cytosine

Insertion - when a base is added

CGG CCC AAT to CGG CGC CAA T

Guanine is added

Deletion - the loss of a base

CGG CCC AAT to CGG CCA A T

loss of Cytosine



Frameshift Mutation

Inserting or deleting one or more nucleotides

Changes the“reading frame” like changing a

sentence

Proteins built incorrectly

Original:

The fat cat ate the wee rat Frame Shift (“a” added):

he fat caa tet hew eer at

Frame shift Mutation



Frame shift Mutation

Amino Acid Sequence Changed

Lec10 Mutation

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