Mendelian inheritance

Question 1

Where does DNA exist?

Answer 1

In the cell nuclei and in the mitochondria.

Question 2

True or false? Most of the DNA codes for proteins.

Answer 2

False. Most of the DNA is so called “junk” DNA with elusive function.

Question 3

How many chromosome pairs does a human normally have?

Answer 3

23 chromosome pairs.

Question 4

What are genes?

Answer 4

The parts of DNA containing information on the structure or expression of a specific protein (or RNA-molecule).

Question 5

What does a nucleotide consist of?

Answer 5

A nucleotide is a molecule consisting of a nitrogenous base, a phosphate group and a sugar. Nucleotides are the building blocks in DNA and RNA.

Question 6

What is an allele?

Answer 6

An allele is one of several forms of a gene.

Question 7

How many alleles are there in the autosomes?

Answer 7

Two. One of the alleles stems from the father and the other from the mother.

Question 8

What is meant by compound heterozygosity?

Answer 8

The presence of two different mutant alleles at a particular gene locus, one on each chromosome of a pair.

Question 9

What can disease causing mutations result in?

Answer 9

Abnormal proteins (loss or gain of function).
Too little (or no) proteins.
Too much proteins.

Question 10

What is a mutation?

Answer 10

Any change to the DNA-sequence.

Question 11

What is a polymorphism?

Answer 11

A genetic variant preserved in the population with a allele frequency of more than 1%. In other words, common genetic variants.

Question 12

How are genetic mutations classified?

Answer 12

Chromosome mutations.
Regional mutations.
Gene mutations.

Question 13

What is a chromosome mutation?

Answer 13

A chromosome mutation is an numerical alteration to the karyotype. Examples of chromosome mutations are monosomy, trisomy or triploidy.

Question 14

What are regional mutations?

Answer 14

Regional mutations are, non-numerical, alterations such as deletions, duplications, translocations, insertions or inversions.

Question 15

What is a gene mutation?

Answer 15

A gene mutation is an alterations to the DNA sequence within a gene. Examples of gene mutations are point mutations (single nucleotide substitutions), or deletions or insertions (affecting one or more nucleotides).

Question 16

What does the term monogenic disorder mean?

Answer 16

Monogenic disorders come as the result of a single defective gene on the autosomes. They are inherited according to Mendel’s Laws (Mendelian disorders).

Question 17

What is a missense mutation?

Answer 17

A mutation in which a single nucleotide replacement results in a codon that codes for an other amino acid.

Question 18

What is a nonsense mutation?

Answer 18

A mutation in which the substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid.

Question 19

What is are insertions and deletions?

Answer 19

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. Deletions are mutations in which a section of DNA is lost, or deleted. Insertions and deletions cause a shift of frame.

Question 20

What are insertions and deletions?

Answer 20

Insertions are mutations in which extra base pairs are inserted into a new place in the DNA. Deletions are mutations in which a section of DNA is lost, or deleted. Insertions and deletions cause a shift in all subsequent codons.

Question 21

What is a splice site mutation?

Answer 21

A genetic alteration in the DNA sequence that occurs at the boundary of an exon and an intron (splice site). This change can disrupt RNA splicing resulting in the loss of exons or the inclusion of introns and an altered protein-coding sequence. Also called splice-site variant.

Question 22

What is a) diagnostic genetic testing, b) presymptomatic genetic testing, c) predictive genetic testing?

Answer 22

Diagnostic testing: Used to identify a spesific genetic or chromosomal condition in an affected individual.

Presymptomatic testing: A test performed on a person who has a family history of disease but no symptoms of the specific disorder at the time of testing.

Predictive testing: Genetic test of an asymptomatic person to predict future risk of disease.

Question 23

If you suspect a genetic disorder in a patient how should start a diagnostic work-up?

Answer 23

Look at the clinical phenotype.

Investigate family history / Pattern of inheritage (using a genogram).

Question 24

If you suspect a genetic disorder in a patient how should start a diagnostic work-up?

Answer 24

Look at the clinical phenotype.

Investigate family history / Pattern of inheritance (using a genogram).

Question 25

Name some tests used for DNA analysis.

Answer 25

PCR (Polymerase Chain Reaction).
SNP-array (Single Nucleotide Polymorphism array).
MLPA (Multiplex Ligation-dependent Probe Amplification).
DNA sequencing.

Question 26

Which DNA analysis test uses a primer to allow exponential amplification of target DNA sequence?

Answer 26

PCR (Polymerase Chain Reaction).

Question 27

Which DNA analysis test is well suited when diagnosing disorders frequently caused by small or large deletions/insertions?

Answer 27

MLPA (Multiplex Ligation-dependent Probe Amplification).

Question 28

Which DNA analysis test requires PCR amplification of the gene to be analysed as a first step?

Answer 28

Sanger DNA sequencing.

Question 29

What kinds of alterations to the DNA can be detected through Sanger DNA sequencing?

Answer 29

Any point mutation and small deletion/insertion.

Question 30

What is the major difference between Sanger sequencing and Next Generation Sequencing (NGS)?

Answer 30

Sanger sequencing has a gene by gene approach (and is therefore time consuming, resource demanding and expensive). NGS allows the sequencing of hundreds of genes from hundreds of patients simultaneously.

Question 31

What is a pedigree / genogram?

Answer 31

A family three showing the pattern of inheritance of a phenotypic trait.

Question 32

What are possible patterns of inheritance?

Answer 32

Autosomal dominant.
Autosomal recessive.
X-linked recessive (/ dominant).
Mitochondrial.

Question 33

True or false: In autosomal recessive diseases men are affected more frequently than women.

Answer 33

False. In autosomal recessive diseases men and women are affected equally as frequent.

Question 34

Name some examples of autosomal recessive genetic diseases.

Answer 34

Cystic fibrosis.

Phenylketoneuria (PKU) (also called Følling’s disease).

Question 35

What is penetrance and expressivity of a genetic diseases?

Answer 35

Penetrance is the number of individuals with a mutation that exhibit clinical symptoms.
Expressivity is differences is phenotype among individuals with a certain genotype.

Question 36

True or false: Men and women are equally as often affected by autosomal dominant genetic diseases.

Answer 36

True. Men and women are affected equally as often.

Question 37

Name some examples of autosomal dominant genetic diseases.

Answer 37

Huntington’s disease.
Marfan syndrome.
Colon polyps.
Myotonic dystrophy.

Question 38

True or false: Mainly men are affected by X-linked recessive diseases. Heterozygous women are never affected by X-linked recessive diseases.

Answer 38

False: Yes, mainly men are affected by these diseases. Generally speaking, women have to be homozygous to be affected, but cases of skewed X-inactivation and Turner syndrome (monosomy X) are exceptions.

Question 39

Name some examples of X-linked recessive diseases.

Answer 39

Hemophilia type A and B.
Duchenne muscular dystrophy.
Fragile X syndrome.

Question 40

What is meant by germline mosaicism?

Answer 40

Mosaicism is when a person has two or more genetically different sets of cells in his or her body. Germline mosaicism is aslo called gonadal mosaicism. It arises through the occurrence of a mutation de novo in a germline cell or one of its precursors during the early embryonic development of the parent.

Question 41

Sometimes genetic diseases occur despite no previous family history of disease. How can this be explained?

Answer 41

Autosomal recessive diseases often have no previous history within the family. Family members can be unaffected carriers. (Same thing for X linked recessive diseases.)

The disease could be caused by a new mutation transmitted by one of the parents, or occurring in the early embryo.

Germline mosaicism in one of the parents could be the cause of the disease.

Low penetrance may result in lack of disease history in a family.