MUTATIONS AND GENETIC DISORDERS

Question 1

Differnce between Variant and Mutation

Answer 1

• Variant – any change in the sequence of the genome.
• Mutation – a variant causing a disease.
• • Mutation can either be harmless or harmful. In some rare cases, it can even be beneficial.

Question 2

Germline Mutation

Answer 2

A mutation carried by the germ cells. Therefore,

can be inherited

Question 3

Somatic Mutation

Answer 3

A mutation occurring in other cells in the body,
that is not passed on to offsprings. This mutation is
often caused by environmental factors (smoke,
chemicals, radiations and so forth).

Question 4

Monogenetic Disorders

Answer 4

Genetic disease that result from single mutated genes.

Question 5

Autosomal dominant disorders

Answer 5

Offspring that inherit at least one copy of the mutated gene will be affected.

• Huntington’s – degenerative brain disorder. Onset age 30-50.
• Familial hypercholesterolemia.
• Multiple endocrine neoplasia

Question 6

Autosomal recessive disorders

Answer 6

Fffspring that carry one of the mutated gene will not be affected.
Only an offspring that carries 2 set of mutated chromosomes will be sick.

• Tay sachs – lack of enzyme hexosaminidase, which breaks down fatty acids in nerve tissues. Symptoms begins at 4-6 months and death comes by 5 years of age.
• Cystic fibrosis – defect in the transport of calcium ions across epithelial, which leads to abnormality viscous mucous secretions. Leads to problem in the lungs and breathing.
  Chromosome 7.
• Sickle cell disease.

Question 7

Sex linked recessive disorders

Answer 7

Mutation on sex chromosome. Most common are 𝑋-linked recessive mutation on the 𝑋-chromosome.

• Vitamin 𝐷 resistance – receptors of this vitamin are resistant. Causes growth retardation, bowing of bones and dental problems.
• Hemophilia – lack of clotting factor 8 (hemophilia 𝐴), or clotting factor 9 (hemophilia 𝐵).
• Color blindness.
• Duchene.

Question 8

𝑋-linked dominant disorders

Answer 8

• Rhett.

* Rickets – deficiency of the receptor of vitamin D.

Question 9

Types of Mutations

Answer 9

We usually differentiate between three types of mutations:
* Chromosomal numeric mutation – when there is a change of the number of chromosomes
present in the genome.
* Chromosomal structure mutations – when there is a change is the structure of the
chromosomes (not it the amount of chromosomes themselves).
* Gene mutation – when there is a change in the 𝐷𝑁𝐴 sequence itself.

Question 10

Chromosomal Numeric Mutations

Answer 10

Refers to any change in the number of the chromosomes.

• Euploidy – the normal state, when there is correct number of each chromosome.
  
  • Diploid in somatic cells.
  • Haploid in germ cells.
• Polyploidy – a state when there are too many sets of chromosomes. These conditions are not viable.
  
  • Triplodity – 69 chromosomes.
  • Tetraploidity – 92 chromosomes.
• Aneuploidy – an incorrect number of copies of a specific chromosome.
• Trisomy – when there are tree copies of a specific chromosome.
• Monosomy – when there is one copy of a specific chromosome
  
  • Monosomy 𝑋𝑂 (Turner syndrome) – these women
    have a characteristic appearance, and
    they tend to suffer from cardiac and renal disorders.

Question 11

Types of Trisomy

Answer 11

Trisomy 21 (down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome) 
Trisomy 𝑋𝑋𝑌 (Klienfelter’s syndrome)
Trisomy 𝑋𝑌𝑌 
Trisomy 𝑋𝑋𝑋

Question 12

Trisomy 21 (down syndrome)

Answer 12

These patients usually suffer mild to moderate mental
retardation. They usually have a characteristic facial appearance, and an enhanced susceptibility to heart disease and Alzheimer’s.

Question 13

Trisomy 18 (Edwards syndrome)

Answer 13

Extra 18th chromosome is apparent. Results in small
jaw and mouth, abnormally shaped small head, clenched fists, rocker bottom feet, low setears, heart defects and mental retardation. 95% of affected die utero and the rest till 3 years of age.

Question 14

Trisomy 13 (Patau syndrome)

Answer 14

extra 12th is chromosome is apparent. Results in severe mental retardation, heart defects, small head, polydactyl cleft palates and lips and neural tube defects. Most affected kids die few weeks after birth.

Question 15

Trisomy 𝑋𝑋𝑌 (Klienfelter’s syndrome)

Answer 15

these are men that suffer from disorders in secondary sexual features. In addition, they sometimes suffer from slight mental retardation

Question 16

Trisomy 𝑋𝑌𝑌

Answer 16

Men usually more aggressive, suffer from severe acne, increased risk of learning disabilities, delayed development of speech and language skills.

Question 17

Trisomy 𝑋𝑋𝑋

Answer 17

causes no unusual physical features. Most women have normal sexual development and are able to conceive. They have increased risk of learning disabilities, delayed development of speech and language skills.

Question 18

Chromosomal Structural Mutations

Answer 18

Any change in the structure of a chromosome that leads to a disorder.

Question 19

Types of changes in the structure of a chromosome that leads to a disorder:

Answer 19

*Deletion – when a large part of a chromosome is missing.
- Cri du chat syndrome – part of the 5th
chromosome is deleted. Causes the infant to
sound like a meowing kitten, due to problems
with the larynx and the nervous system. Sick
infants may suffer from growth problems and
mental retardation.

• Duplication – when a large piece of a chromosome is duplicated.
• Translocation – when large pieces of none homologous chromosomes are swap places.
  - A translocation between chromosomes 9 and
  22 often leads to a type of blood cancer called
  chronic myeloid leukemia (𝐶𝑀𝐿).
  - A translation between chromosomes 14 and 21,
  4% of down syndrome occurs
• Inversion – when a large piece of a chromosome is placed in a wrong orientation backwards.

Question 20

Gene Mutation

Answer 20

A change in the 𝐷𝑁𝐴 sequence that affects only one gene – insertion and deletions of several nucleotides,
or substitution of one base (point mutation).

Question 21

Point mutation

Answer 21

Substitution of one base (letter).
* Synonymous (silent) – a change of a base that creates a different codon that codes the
same amino acid.
* Missense – a new codon that encodes for a different amino acid.
* Nonsense – a new codon that encodes to a stop codon. This is the most devastating point
mutation.

Question 22

Insertions/Deletions

Answer 22

Can either be in frame or frame shift.

• In frame – an insertion or a deletion of a number of bases that can be divided by 3 (does
  not change the pattern of the original codons, but makes an addition/deletion of new
  codons in the sequence).
• Frame shift – an insertion of deletion of any other number that is not divided by 3 (changes
  the original pattern by altering the original codons). It is the more devastating type of mutation.