genetic disease

Question 1

What is a genetic disease?

Answer 1

A genetic disease is a disease that is caused by an abnormality in an individual’s DNA
Most genetic disorders are quite rare
Genetic disorders may or may not be inherited (passed down from the parents to offspring)
In non-heritable genetic disorders, defects may be caused by somatic mutations - changes to the DNA of somatic cells after the birth
The defect can only be heritable if genetic disorder occurs in the germ line

Question 2

What are the four types of genetic disorders?

Answer 2

1.Single gene defects
2.Chromosome abnormalities
3.Multifactorial disorders
4.Cancer

Question 3

What are the traits of single gene disorders?

Answer 3

*Mutations can lead to a gain-of-function but also to a loss-of-function
*A condition that is present from birth (congenital)
*gene mutation may be passed between generations if present at birth or arise in germ cells of a parent

Question 4

What are the types of mutations?

Answer 4

*Missense mutation
*nonsense mutation
*silent mutation
*frameshift mutations
*promoter mutations/ other regulatory sequences

Question 5

What is a missense mutation?

Answer 5

▪These are base changes that alter the codon for an amino acid resulting in its replacement with a different amino acid

Question 6

What is a nonsense mutation?

Answer 6

▪Base changes that convert an amino acid codon to a stop codon, resulting in a premature termination of translation and the production of a shortened protein

Question 7

What is a silent mutation?

Answer 7

do not cause any change in an amino acid

Question 8

What is a frameshift mutation?

Answer 8

▪These mutations result from the insertion or deletion of one or more bases causing the alteration of the reading frame of the gene and a different set of codons, leading to an altered protein

Question 9

What is a promoter/ other regulatory sequence mutation?

Answer 9

▪Affect the way gene transcription is regulated, often abnormally reducing or enhancing the expression of certain genes

Question 10

What are some examples of single gene inherited diseases?

Answer 10

• sickle cell anemia
• cystic fibrosis
• huntington’s disease
• duchenne muscular dystrophy

Question 11

What do chromosomal abnormalities lead to?

Answer 11

*Some chromosomal abnormalities result in miscarriage or stillbirth

*50% of spontaneous miscarriages are chromosomally abnormal

Question 11

What are the two groups that chromosome abnormalities can be sorted into?

Answer 11

• numerical abnormalities
• structural abnormalities
  (chromosome structure altered)

Question 12

What is a numerical abnormality?

Answer 12

When an individual is missing either a chromosome from a pair (monosomy) or has more than two chromosomes of a pair (trisomy)

Question 13

What does euploid mean?

Answer 13

Euploid is the correct number of chromosomes in a species

Question 14

What does aneuploid mean?

Answer 14

Aneuploid is the change in the chromosome number

Question 15

What do chromosomal abnormalities cause?

Answer 15

nondisjunction during meisosis and mitosis

Question 16

What is trisomy? (extra or less chromosomes)

Answer 16

*Occurs when an individual has three of a particular type of chromosome

Question 17

What are the characterisitics of downsyndrome? trisomy21

Answer 17

▪short stature
▪eyelid fold
▪flat face
▪stubby fingers
▪wide gap between first and second toes

Question 18

What are the characterisitics of triosmy13/ patau syndrome?

Answer 18

Affect 1/12,000 live births
*Children do not live more than a few months
▪mental deficiency
▪severe central nervous malformations
▪sloping forehead, malformed head
▪scalp defect

Question 19

What are the characteristics of trisomy18/ Edward syndrome?

Answer 19

Second most common trisomy (1/6,000)
*Children do not live more than a few months
▪a small, abnormally shaped head
▪a small jaw and mouth
▪delayed growth

Question 20

What are the characteristics of klinefelter syndrome (XXY Trisomy)?

Answer 20

▪
Male with underdeveloped testes and prostate; some breast overdevelopment
▪
Long arms and legs; large hands
▪
Near normal intelligence
▪
No matter how many X chromosomes, presence of Y renders individual male

Question 20

What are the characteristics of the XO turner syndrome (monosomy 2n-1)? (sex chromosomes)

Answer 20

▪Female with a single X chromosome, the other X chromosome is missing or partially missing (in 25% of cases, it could be due to structural alterations)
▪Short, with broad chest and widely spaced nipples
▪Can be of normal intelligence and function with hormone therapy
▪Life expectancy is normal in most cases (depends on the severity of malformations)

Question 21

What are some chromosomal structural abnormalities?

Answer 21

*Deletions
*Duplications
*Inversions
*Translocations

Question 22

What are deletions?

Answer 22

A portion of the chromosome is missing or deleted
▪One or both ends of a chromosome breaks off
▪Two simultaneous breaks lead to loss of an internal segment

Question 23

What are some diseases caused by deletions?

Answer 23

➢Cri du chat syndrome - chromosome 5 deletion - (1 / 50,000)
➢Wilms tumor with aniridia - chromosome 11 deletion - (1 / 60,000)

Question 24

What are duplications?

Answer 24

A portion of the chromosome is duplicated, resulting in extra genetic material.
▪Presence of a chromosomal segment more than once in the same chromosome

Question 25

What is a disease caused by duplications?

Answer 25

➢Charcot-Marie-Tooth disease type 1A – duplication of a gene (PMP22) on chromosome 11

Question 26

What is inversion?

Answer 26

A portion of the chromosome has broken off, turned upside down, and reattached. As a result, the genetic material is flipped/inverted
▪Genes occur in reverse order in inverted segment

Question 27

What is a translocation?

Answer 27

A portion of one chromosome is transferred to another (non-homologous) chromosome.

▪It can be reciprocal (also known as Robertsonian) or not (or insertion)

▪The Robertsonian one follows breakage of two nonhomologous chromosomes and improper re-assembly

Question 28

What is an example of multifactoral disorders?

Answer 28

diabetes type 2
▪The disease is characterised by high sugar levels in the blood

▪It has a high frequency in many families though there is no evidence of any pattern of Mendelian inheritance

➢Hypercholesteremia, hypertension, obesity, etc

Question 29

What is cancer?

Answer 29

Cancer is a genetic disease, also influenced by environmental and lifestyle factors, at a somatic level (somatic cells) resulting from mutated or abnormally expressed genes

▪Most cancers are somatic that are not passed to offspring

▪Only 1% due to germ-line mutations (cancer can be inherited from parents)

Question 29

What are the two fundemental properties of cancer cells?

Answer 29

➢unregulated cell proliferation
➢metastatic spread

Question 30

What is step 1 of cancer?/ activating + increasing the expression of oncogenes

Answer 30

Activation of proto-oncogenes (normal) to oncogenes (hyperactive)
▪Proto-oncogenes in normal cells stimulate cell growth and division, in response to specific signals
▪In cancer, they become permanently switched on (even without specific signals)

Question 31

What is step 2 of cancer?/ inactivating tumor suppressor genes

Answer 31

Inactivating tumor suppressor genes
▪
In normal cells, they block/regulate cell division at checkpoints, if cells are not ready to go on (to allow extra growth, DNA repair if it damaged, etc)
▪In normal cells, they also initiate the process of apoptosis
▪In cancer, they are permanently switched off

Question 32

How can cancer spread?

Answer 32

*Cancer invades and colonises surrounding tissues, normally reserved for other kinds of cells
▪Cancer becomes malignant
*Finally, cancer can metastasises to distant sites (through the bloodstream or lymphatic vessels) and form a secondary tumour
▪The more widely the cancer spreads, the harder it is to eradicate