Nomenclature of genetic variant and methods

Question 1

What are the three types of disorders that the candidate should be able to point out?

Answer 1

• Monogenic disorders
• Polygenic disorders
• Chromosomal disorders

Question 2

What early developmental genetics process should candidates demonstrate knowledge about?

Answer 2

Gastrulation

Question 3

What are the principles for methods of genetic diagnosis?

Answer 3

• Gene tests
• Cytogenetic methods

Question 4

What is the focus of cancer genetics in medical genetics?

Answer 4

Study of hereditary cancers and their genetic basis

Question 5

Fill in the blank: The study of genetic variants that modify human responses to pharmacological reagents is called _______.

Answer 5

Pharmacogenetics

Question 6

What are the two main types of genetic diseases mentioned?

Answer 6

• Chromosomal disorders
• Single gene disorders

Question 7

What is the Hardy-Weinberg equilibrium used for?

Answer 7

To calculate frequencies of disease variants

Question 8

How are mutations in proteins typically classified in molecular genetics?

Answer 8

• Loss of function
• Gain of function

Question 9

True or False: About 5-10% of cancers are inherited.

Answer 9

True

Question 10

What is the most important enzyme in the cytochrome P450 superfamily?

Answer 10

Cytochrome P450 2D6 (CYP2D6)

Question 11

What does the term ‘multifactorial diseases’ refer to?

Answer 11

Diseases that involve genetics, lifestyle, and environmental factors

Question 12

What is the significance of next generation sequencing (NGS) in medical genetics?

Answer 12

It allows for high-throughput sequencing and reduced costs

Question 13

Who is considered the ‘father’ of genetics?

Answer 13

Gregor Mendel

Question 14

What is the first human disease attributed to genetic causes?

Answer 14

Alkaptonuria

Question 15

What are the types of inheritance patterns for single gene disorders?

Answer 15

• Recessive
• Dominant
• X-linked
• Mitochondrial

Question 16

What is the role of genetic counselling?

Answer 16

To provide advice and information about genetic disorders

Question 17

Fill in the blank: Genetic variants that affect drug metabolism can lead to _______ metabolizers.

Answer 17

Slow, rapid, or ultra rapid

Question 18

What type of disorders can result from enzyme defects in the urea cycle?

Answer 18

Metabolic disorders

Question 19

What is the focus of developmental genetics?

Answer 19

Genes important for embryo development

Question 20

What is the common phenotype associated with alkaptonuria?

Answer 20

Black urine

Question 21

What is the main advantage of long-read sequencing?

Answer 21

May detect variants not detected by NGS

Question 22

What does the abbreviation ‘c.’ represent in genetic nomenclature?

Answer 22

Coding DNA reference sequence.

It indicates that the variant is described at the DNA level.

Question 23

What does the abbreviation ‘g.’ signify in genetic nomenclature?

Answer 23

Genomic DNA reference sequence.

It indicates that the variant is described in the context of the entire genome.

Question 24

What is an example of a reference sequence version number?

Answer 24

NM_000551.4

Different versions may represent different numbers of amino acids.

Question 25

How is a nucleotide substitution described in genetic nomenclature?

Answer 25

X>Y ## Footnote Example: c.76A>C indicates that nucleotide 76 changed from A to C.

Question 26

What is the abbreviation for an insertion in genetic nomenclature?

Answer 26

"ins" ## Footnote It is used after the nucleotides flanking the insertion site.

Question 27

What does 'del' indicate in genetic nomenclature?

Answer 27

Deletion of nucleotides. ## Footnote Example: c.76_78del indicates deletion between nucleotides 76 and 78.

Question 28

What does 'r.' signify when describing RNA variants?

Answer 28

Indicates the change at the RNA level. ## Footnote RNA changes are quoted similarly to DNA variants.

Question 29

What does the abbreviation 'p.' represent in genetic nomenclature?

Answer 29

Protein reference sequence. ## Footnote It indicates that the variant is described at the protein level.

Question 30

What is the purpose of the Human Genome Variation Society (HGVS) nomenclature?

Answer 30

To prevent misinterpretation of variants in DNA, RNA, and protein sequences. ## Footnote It is widely used in clinical diagnostics.

Question 31

What are the five classes of variant classification?

Answer 31

* 1: does not affect function (normal) * 2: probably does not affect function * 3: unknown (VUS) * 4: probably affects function * 5: affects function (pathogenic) ## Footnote This classification helps in determining the significance of genetic variants.

Question 32

How are silent mutations described in genetic nomenclature?

Answer 32

They must be described at both DNA and protein levels. ## Footnote Example: p.Leu54Leu must also indicate the corresponding DNA change.

Question 33

What is a frame shift mutation?

Answer 33

A mutation caused by insertion or deletion of nucleotides not divisible by three. ## Footnote This alters the reading frame of the gene.

Question 34

What is the significance of MANE Select in clinical reporting?

Answer 34

It consists of one transcript at each protein-coding locus that is representative for clinical reporting. ## Footnote It serves as a universal standard for genomic resources.

Question 35

What is the standard for indicating a stop codon in protein nomenclature?

Answer 35

* or Ter ## Footnote It signifies the end of translation in protein sequences.

Question 36

What does it mean if a variant is classified as 'VUS'?

Answer 36

Variant of unknown significance. ## Footnote This indicates that the impact of the variant on health is not yet determined.

Question 37

What are the two types of sequence variants that can affect protein function?

Answer 37

* Loss of function (LOF) * Gain of function (GOF) ## Footnote Understanding these mechanisms is critical for interpreting genetic variants.

Question 38

What are the consequences of sequence variants?

Answer 38

* Truncated non-functional protein * Change in structure or conformation of protein * Unstable mRNA (no protein) * Nonsense mediated-mRNA decay (NMD) ## Footnote These consequences can lead to various diseases or conditions.

Question 39

What does 'c.[76A>C];[87delG]' indicate?

Answer 39

Two sequence changes in different alleles. ## Footnote This format is used for recessive diseases.

Question 40

What is the primary role of the software and databases like gnomAD?

Answer 40

To provide frequency of variants. ## Footnote This helps researchers understand the prevalence of genetic variants in populations.