Lecture 6 - Human Genetics Part 2

Question 1

What are some ways genetics can cause disease?

Hint: we looked at 6 ways.

Answer 1

1. Recessive allele expression.
2. Single dominant allele expression.
3. Polygenic inheritance - which is influenced by the environment.
4. Sex-linked inheritance.
5. Chromosomal anomalies.
6. Regulator gene defects.

Question 2

What is Tay Sachs Disease and which populations have a higher incidence of this disease?

Answer 2

Tay Sachs disease is a fatal autosomal recessive disease caused by a mutation in the HEXA gene, which prevents the functional expression of this gene. The HEXA gene encodes for an enzyme that is required for the break down of certain fatty substances. Due to the absence of this enzyme there is a build of fatty substances in the brain and spinal cord which eventually lead to death in infancy or early childhood.

Populations with a decreased genetic pool are at higher risk of passing on Tay Sachs disease to their children. Some of these populations include Ashkenazi Jewish people, Irish-American people, and French Canadian people.

Question 3

How has screening for the HEXA mutation affected incidence of Tay Sach’s disease in at-risk populations?

Answer 3

Screening for Tay Sach’s disease in Ashkenazi jewish populations has decreased number of children with the disease by 90%.

Question 4

What is Huntington’s disease?

Answer 4

Huntington Disease is an autosomal dominant disorder characterisised by CAG repeat of over 40 in the Hungtington gene.

Question 5

What increases severity of Huntington’s disease?

Answer 5

A smaller gene pool.

Question 6

Inheritance of the mutation of the Huntington gene from which parent increases risk of earlier onset of Huntington’s disease?

Answer 6

Inheritance from the father.

Question 7

What is an example of a disease or disorder that has polygenic inheritance?

Answer 7

Schizophrenia and cancer.

Question 8

What is fragile-X syndrome?

Answer 8

Fragile X syndrom is a sex-linked disorder characterized by a CGG repeat in the FMR1 gene that silences the gene, which is located on the X chromosome. FMR1 gene encodes for a protein that is important for brain plasticity.
XY karyotypes are more likely to be affected by this mutation as they only have one X chromosome and therefor cannot rely on a functional FMR1 gene on the other X chromosome.

Question 9

Which karyotype (XX or XY) is more at risk of being affected by the mutation which gives rise fragile-X syndrome?
Explain why.

Answer 9

The XY karyotype.

Question 10

What are two ways genetic screening can be used to prevent the transmission of and/or presentation of gentics-based diseases or disorders?

Question 11

What is PKU and what can individuals with this disease do to prevent the negative effects of this disease?

Question 12

What is the role of regulator genes?

Answer 12

Regulator genes control the switching on and off of genes.

Question 13

In regards to gene expression what does the term “range of reaction” refer to?

Hint: phenotype

Answer 13

Range of reaction refers to the range of possible expressions/phenotypes from a genotype.

Question 14

What is the epigenome?

Answer 14

The epigenome refers to the set of chemical compounds that dictate gene expression and/or repression. The epigenome is heritable, but reversible as well, unlike the genome or DNA.

Question 15

What are three mechanisms involved in gene regulation?

Answer 15

1. Histone modification.
   2.DNA methylation.
   3.microRNA

Question 16

How does histone modification regulate gene expression?

Question 17

How does DNA methylation regulate gene expression?

Question 18

How does microRNA regulate gene expression?

Question 19

What disease is caused by a mutation in the HEXA gene?

Answer 19

Tay Sachs disease is caused by a mutation in the HEXA gene. This gene encodes for an enzyme that helps break down harmful fatty substances. If there is a mutation in this enzyme such that it cannot function, which is the case in Tay Sachs, then there is a build up of fatty substances in the brain and spinal cord which becomes fatal during infancy and early childhood.
Tay Sachs is a fatal autosomal recessive disease, which means in develops if you have two recessive alleles that are the fatal mutation for this gene.

Question 20

What are some genetic disorders/diseases that we studied that are related to chromosomal anomalies?

Answer 20

Down Syndrome (trisomy 21 - 3 copies of the autosome 21)
Klinefelter Syndrome (XXY)
Turner Syndrome (XO - only one X chromosome and no Y chromosome)

Question 21

What is Huntington’s Disease?

Answer 21

Huntington’s Disease is an autosomal dominant disease where there is a repeat of >40 repeats of a trinucleotide sequence in the Huntington gene of CAG.

Question 22

What is the biochemical mechanism underlying Huntington’s disease?

Answer 22

The Huntington gene encodes for a protein called Huntingitn. Huntingtin is thought to play a key role in neuronal and astrocyte function in the brain, although exactly what it does is unknown.
CAG encodes for the amino acid glutamine. The CAG repeats seen in huntingtin’s disease cause an abnormal chain of glutamine in the huntington protein, which prevents it from functioning correctly. This results in damage to neurons and astrocytes in the brain, which leads to, among other things, cognitive deterioration.