Genetic Basis Of Disease

Question 1

How are diseases classified?

Answer 1

Those environmentally determined
Those genetically determined
Those both environmentally and genetically determined

Question 2

What are the classifications of mutations?

Answer 2

Genomic mutations
Chromosomal mutations
Gene mutations

Question 3

What are genomic mutations?

Answer 3

Loss or gain of whole chromosomes giving rise to monosomy or trisomy.

Question 4

What are chromosomal mutations?

Answer 4

Rearrangements of genetic material causing visible structural changes in the chromosomes

Question 5

What are gene mutations?

Answer 5

Submicroscopic mutations causing partial or complete deletion of a gene or more often affect a single base pair

Question 6

What are the categories of genetic disorders?

Answer 6

Single gene disorders
Multifactorial disorder
Cytogenetic disorders

Question 7

What are patterns of inheritance for single gene disorders?

Answer 7

Autosomal dominant
Autosomal recessive
X linked

Question 8

Explain autosomal dominant disorders

Answer 8

They are manifested in the heterozygous state. At least one parent of an index case is usually affected but occasionally an index case may be a new mutation in the germ cells of either parent.

The siblings of such patients are neither affected nor have an increased risk of developing the disease.

Question 9

What is reduced penetrance?

Answer 9

This is when some individuals inherit the mutant gene and are phenotypically normal.

50% penetrance means that 50% of those who carry the gene express the trait.

Question 10

What is variable expressivity?

Answer 10

This is when a trait is seen in all individuals who carry the mutant gene but is expressed differently among individuals.

Question 11

What mutations autosomal dominant disorders lead to?

Answer 11

Loss of function mutations (reduced production of a gene product)
Gain of function mutations (give rise to an inactive abnormal proteins)

Question 12

What type of proteins does loss of function mutation clinically manifest with?

Answer 12

Regulatory proteins
Key structural proteins (subunits if multimeric proteins)

Question 13

What happens in gain of function mutations?

Answer 13

The gene product acquires properties not normally associated with the normal gene. It affects normal proteins with toxic properties

Question 14

Examples of autosomal dominant disorders

Answer 14

Neurofibromatosis, Huntington disease, adult polycystic kidney disease, Marfan syndrome, von willebrand disease

Question 15

What are the chances of occurrence in autosomal recessive disorders?

Answer 15

25% for each birth

Question 16

Characteristics of autosomal recessive disorders?

Answer 16

Complete penetrance is more common
It is early onset
Heterozygous are almost always normal phenotypically and clinically
It includes almost all inborn errors of metabolism
If the mutant gene has a low frequency in the population, it is likely that the proband is from a consanguineous marriage.

Question 17

Examples of autosomal recessive disorders

Answer 17

Sickle cell anemia
Thalassemias
Congenital adrenal hyperplasia
Neurogenic muscular atrophies
Infantile polycystic kidney disease

Question 18

What can cause partial expression of an X linked recessive disorders in females?

Answer 18

Lyonization

Question 19

Examples of X linked disorders

Answer 19

G-6-PD deficiency
Fragile X syndrome
Haemophilia A and B
Wiskott-Aldrich syndrome
Diabetes insipidus

Question 20

What are multifactorial disorders?

Answer 20

They are disorders that result from the combined effect of environmental factors and two or more mutant genes.

Question 21

Examples of multifactorial inheritance.

Answer 21

Cleft lip/palate
Gout
Diabetes mellitus
Pyloric stenosis
Hypertension
Congenital heart disease
Coronary heart disease

Question 22

What are some common forms of alteration in chromosomal structure?

Answer 22

Translocation
Deletion
Inversion
Isochromosomes
Ring chromosomes (a type of deletion)

Question 23

What is aneuploidy?

Answer 23

This is when an exact multiple of haploid chromosomes is not present. Basically, a cell has a missing or extra chromosome.

It is seen when an error occurs in meiosis or mitosis and a cell acquires a chromosome complement not an exact multiple of 23.

Question 24

Causes of aneuploidy

Answer 24

Nondisjunction (ch does not separate properly)
Anaphase lag

Question 25

What is mosaicism?

Answer 25

It occurs when mitotic division in early development gives rise to two or more populations of cells in the same individual.

Question 26

Cytogenetic disorders involving the auto-aimed

Answer 26

Down syndrome (21)
Patau syndrome (13)
Edward syndrome (18)

Question 27

Cytogenetic disorders involving the sex chromosomes

Answer 27

Klinefelter syndrome
Turner syndrome
XYY syndrome

Question 28

What is an isochromosome?

Answer 28

This is when one arm of chromosome is lost and the remaining arm is duplicated resulting in a chromosome consisting of two short arms only or of two long arms.

The genetic information is the exact same on both arms.

Question 29

What are the diagnostic biopsy of the human genome methods available

Answer 29

Polymerase chain reaction (PCR)
Flow cytometry
Fluorescent in situ hybridisation
Filter hybridisation