Genetics

Question 1

Describe DNA structure and function, including mitochondrial DNA

Answer 1

DNA is a double helix structure made up of nucleotides which consists of a Phosphate a sugar and a base, The double helix structure is joined by base where A is alwayus joined to T. and G is always joined to C.

Functions
- Storage of information
-DNA replication
-Transcription and translation
-Inheritance

MtDNA is the DNA that is inherited only from the mother and has a high mutation rate. it encodes 37 genes.

it primarily functions to generate ATP via OXPHOS(oxidative phosphorylations) . Secondary functions include iron homeostasis, metabolic processes, apoptosis and programmed cell death, ROS production and consumption.

Question 2

Describe RNA structure and function

Answer 2

RNA is a single stranded sugar phosphate. it is divided into three types. mRNA, tRNA, rRNA

the primary function of RNA is making proteins through translation. It also functions in gene regulation RNA editing and RNA interference

Question 3

Explain how DNA is packaged in the nucleus

Question 4

Explain the process of transcription and translation

Answer 4

Transcription is the process of turning DNA into mRNA. Occurs through the process of initiation, elongation and termination. Genes involved in this process are called transcription factors.

Translation is the process of turning mRNA into protein.it occurs in the cytoplams.
The mRNA becomes associated with ribosomes which of consists of rRNA. The mRNA and the tRNA binds the codons together forming a polypeptide chain. thus this undergoes post translation modification to become a protein.

Question 5

Describe the cell cycle, including mitosis and meiosis

Answer 5

G0-Cell cycle is at rest.
G1- cellular content, EXCLUDING chromosomes are du.plicated here.
S- Each of the 46 chromosomes is duplicated by the cell.(DNA Replication)
G2- Here the cell double checks the duplicated chromosomes making any needed needed repairs.

Mitosis- Follows IPMAT and leads to the formation of body cells

Meiosis- Follows IPMAT, but this process happens twice and it leads to the formation of gamate

Question 6

Describe the DNA replication

Answer 6

This is the process in which a DNA molecule is duplicated before a cell divides. It starts with the seperation of the two complementary strands from available nucleotides then the building of new complementary nucleotides follows. this is essential for cell reproduction and inheritance.

Question 7

List the outcomes of the human genome project

Answer 7

Information
-6 billion base pairs
-99.9% inter-individual homology( only 0.1% of the DNA sequence varies from person to person)
-2% protein coding genes
- 21 000 genes(4368 morbid)
-dark geneomic material
45% viral origin

Question 8

Explain the different chromosomal and single variants and how they contribute to disease

Question 9

Describe the value of taking a family history

Answer 9

Helps with genetic diagnosis
Helps understand genetic contributors
Helps build rapport
Helps understand psychosocial factors
Helps understand pattern of inheritance
Allows risk to be shared in context
Identifies family members who could benefit form intervention

Question 10

Explain why mitochondrial inheritance is only maternal

Question 11

Be able to construct a three-generation pedigree using standard symbols

Question 12

Apply principles of mendelian inheritance to identify the mode of inheritance in a family and asses risk for as yet unaffected individuals

Question 13

Describe how heteroplasmy influences expression and transmission in mitochondrially inherited disease

Answer 13

This refers to the presence of more than one type of mitochondrial DNA within an individual’s cells. Heteroplasmy can influence the phenotype, with the proportion of mutant mitochondria affecting the severity of symptoms.

Question 14

Discuss the concept of genomic imprinting

Answer 14

Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the mother or the father

Question 15

Explain how genomic imprinting can affects a phenotype depending on the parent of origin of a genetic abnormality

Answer 15

So if both copies of an imprinted gene are present ;
one from mom, one fromdad and..
the correct one is “on” and the correct one is “off”….
All is well but…
If one copy missing (deletion) or
has a a pathogenic variant influencing function(single gene disorder)
or both come form one parent with their expected pattern (uniparental
disomy)
or something is wrong with the switch (imprinting centre abnormarity) …….
Then all is not so well - phenotype will depend on which parental chromosom
the problem is on

Question 16

Explain what uniparental disomy is and how it can causse genetic disorders

Answer 16

this is when both copies on an imprinted gene come from one parent with their expected gene.

Question 17

Describe what a triplet repeat disorder is

Answer 17

A triplet repeat disorder is a type of genetic disorder characterized by the abnormal expansion of a sequence of three nucleotides (a triplet repeat) within a gene

Question 18

Discuss the effect of a “dynamic” mutation in terms of risks to future generations

Answer 18

A “dynamic” mutation refers to a type of mutation that exhibits instability and variability in the number of repeats within a particular DNA sequence. These mutations often involve repetitive sequences of nucleotides, such as trinucleotide repeats. The dynamic nature of these mutations means that the number of repeats can change, either increasing or decreasing, as the DNA is passed from one generation to the next.

The effect of dynamic mutations on future generations can present several risks:

Genetic Anticipation: Dynamic mutations are associated with genetic anticipation, a phenomenon where the severity of the disorder tends to increase and the age of onset tends to decrease in successive generations. This is because the number of repeats tends to expand as it is passed from parent to offspring, leading to earlier onset and more severe symptoms in affected individuals.

Increased Disease Severity: As the number of repeats increases beyond a certain threshold, the risk of developing the associated disorder or disease may also increase. This means that individuals inheriting the expanded repeat from affected parents may be at greater risk of experiencing more severe symptoms or developing the disorder earlier in life.

Interference with Gene Function: Dynamic mutations can interfere with the normal function of the gene in which they occur. Depending on the specific gene affected and the nature of the mutation, this interference can disrupt essential cellular processes, leading to the signs and symptoms associated with the disorder.

Transmission of Expanded Repeats: Individuals carrying dynamic mutations may pass on expanded repeats to their offspring. The degree of expansion may vary from generation to generation, further increasing the risk of disease manifestation and severity in future generations

Question 19

Explain the difference between somatic and germline mosaicism

Answer 19

Somatic Mosaicism: Somatic mosaicism refers to the presence of different genetic mutations or variations within the cells of an individual’s body. These mutations are not present in the germline (sperm or egg cells) and therefore are not passed on to offspring. Somatic mosaicism can arise during early embryonic development or later in life and may result in the presence of cells with different genetic profiles within the same individual.

Germline Mosaicism: Germline mosaicism refers to the presence of genetic mutations or variations specifically within the germ cells (sperm or egg cells) of an individual. These mutations may not be present in the somatic cells of the individual but can be passed on to offspring. Germline mosaicism can result in the transmission of genetic disorders or predispositions to future generations even when the parents themselves do not exhibit the disorder or condition.

Question 20

Discuss the various techniques that can be
used to study genetic material

Answer 20

We havr 3 broad categories of testing, Cytogenetic, Molecular cytogenetics and molecular. Under each broad categorie we have certain test that we fall under it.

Cytogenetic
Karyotype
FISH

molecular cytogenetics
QFPCR
Micro-array
MLPA

Molecular
Sanger sequencing
Next generation sequencing

Cytogenetic and Molecular cytogenetics investigate the structure and function of chromosomes

Molecular investigates the structure and function of genes at a molecular level.

Question 21

Describe the cytogenetic techniques which
can be used to visualise chromosomes and
when each should be applied

Answer 21

We have 2 types of cytogenetic techniques, Karyotype and Fish.

FISH- Determines the presence or absence of discrete segments of DNA using fluorescently labelled probes. Only applicable when you know what you are looking for.

Karyotype- Analysis of all 46 chromosomes for large structural or numerical abnormalities. should be used when we want to see all of the chromosomes.

Question 22

Differentiate between diagnostic, carrier,
prenatal and predictive testing

Answer 22

Diagnostic test- This test confirms or excludes a condition
Carrier-
Carrier testing is a type of genetic testing used to identify individuals who carry a genetic mutation for a specific inherited disorder, even though they may not show any symptoms of the disorder themselves. The purpose of carrier testing is to assess the risk of passing on a genetic disorder to future children
Prenatal- Diagnostic testing during a pregnancy to test fetus

Predictive- Offered in the setting of no current signs or symptoms of a genetic condition

Question 23

Discuss the role of population screening

Answer 23

This is the process whereby a whole population, or identified subset is testing for a specific genetic condition. e.g. testing for a high risk condition (covid).

Reduces Disease Burden: By identifying at-risk individuals early, screening reduces the burden of disease on both the community and affected individuals (illness and death).
Early Detection: Screening detects diseases earlier than if there were no screening, leading to better health outcomes.
Empowers Choices: It enables individuals to make informed choices about further tests and treatment, thereby reducing associated problems or complications2.

Question 24

Describe how variants are assigned
significance

Answer 24

Benign>99%
Likely benign 90-98%
VUZ 11-89% uncertainty
likely pathogenic 90-98%
pathogenic->99%

Question 25

Linking individual, family tree, genetic lineage
(ancestral origins) reflecting geographic origin

Answer 25

We all came out of Africa

Question 26

Understanding genetic differences as a result
of geographic location/population selection

Answer 26

Sickle cell anaemia very common in Africa and
other developing regions (Asia) together with
Thalassemia
* Albinism in certain African populations
* Certain cancers more prevalent in some
populations (specific mutations) – spread
around the world (specific BRCA1 mutations in
Ashkenazi Jews)
* Cystic fibrosis more common in Caucasians

Question 27

Actively pursuing (at-risk) genetic lineages as a
public health measure (revisiting inherited
cancers)