[FMS] MCG - genetic basis of disease

Question 1

what is a genome

Answer 1

an organism’s complete set of DNA.

Question 2

what is a gene

Answer 2

a distinct sequence of nucleotides representing the unit of genetic information.

Question 3

what is an allele

Answer 3

each of two or more alternative forms of a gene that arise by variation.

Question 4

what is genetic variation

Answer 4

a change in the nucleotide sequence of the DNA

Question 5

what is SNV?

Answer 5

Single Nucleotide Variant: a difference in a single nucleotide.

Question 6

what is CNV?

Answer 6

Copy Number Variant: Insertion, deletions, inversion and duplications of greater than 1,000 nucleotides.

Question 7

what is chromosomal variation?

Answer 7

variation in chromosome number, multiple sets of chromosome.

Question 8

what is a common variant?

Answer 8

MAF >1% ( minor allele frquency more than 1) in the general population.

Question 9

what is another name for common variants

Answer 9

Single Nucleotide Polymorphisms, SNPs

Question 10

can SNPs be synonymous?

Answer 10

SNPs can be Synonymous (same AA) or non- Synonymous (≠AA).

Question 11

what is a rare variant?

Answer 11

MAF<1%. (minor allele frequency less than 1) When pathogenic, they also named mutations.

Question 12

can mutations be a missense or nonsense?

Answer 12

BOTH -Mutations can be missense (≠AA), nonsense (stop codon).

Question 13

which part of the genome do common and rare variants occur?

Answer 13

non coding region of genome

Question 14

what is a mendelian disease?

Answer 14

AKA Single Gene disease
Disorder caused by abnormality or mutation in the sequence of one gene.

Question 15

What is a multifactorial disease?

Answer 15

AKA Complex disease
Caused by a combination of SNPs in multiple genes and the influence of the environment

Question 16

what is a chromosomal disease?

Answer 16

Abnormalities in chromosome structure or extra copies

Question 17

where does a mitochondrial disease take place?

Answer 17

Caused by a mutation in the non chromosomal DNA of the mitochondria.

Question 18

give 2 examples of mendelian disease

Answer 18

Cystic fibrosis, Huntington disease.

Question 19

give 2 examples of multifactorial disease

Answer 19

psoriasis, Chron’s disease.

Question 20

give an example of chromosomal disease

Answer 20

Trisomy 21 = Down Syndrome

Question 21

give an example of mitochondrial disease

Answer 21

mitochondrial myopathy

Question 22

when comparing Mendelian diseases and complex diseases.- how many genes does it affect

Answer 22

mendelian = single gene
complex = polygenic

Question 23

when comparing Mendelian diseases and complex diseases.- which one is common, and which is rare

Answer 23

mendelian = rare
complex = common

^remember complex is more common since its also influenced by the environment

Question 24

when comparing Mendelian diseases and complex diseases.- whats the penetrance like? (penetrance meaning how many people show the symptoms)

Answer 24

mendelian = high penetrance
complex = variable penetrance

Question 25

what kind of disease can be autosomal dominant, recessive, or x-linked?

Answer 25

Mendelian diseases

Question 26

what does it mean in Cystic fibrosis if the CFTR has a mutation on ΔF508

Answer 26

deletion of 3 nucleotides, resulting in the loss of the amino acid phenylalanine (F) at the 508th position on the protein.

Question 27

where is CFTR located?

Answer 27

Located on q31.2 locus of chromosome 7

Question 28

what does CFTR code for?

Answer 28

It encodes for a chloride ion channel

Question 29

how does the mutation in CFTR affect its function?

Answer 29

Mutations in CFTR reduce the ion channel’s functioning: the protein is misfolded and trapped in the endoplasmatic reticulum and when it manages to reach the cell membrane is not active

Question 30

drugs for CF

Answer 30

Ivacaftor (2012) Ivacaftor-lumacaftor (2015) Ivacaftor-tezacaftor (2018) Ivacaftor-tezacaftor-elexacaftor (2019)

Question 31

biologically, what leads to Huntingtons disease?

Answer 31

Expansion of the Short Tandem Repeat CAG

Question 32

in GWAS what is the association based on?

Answer 32

**based on p-values** **lower P-value = stronger association** between a variant and a disease

Question 33

what does GWAS identify?

Answer 33

identify **SNPs** - HOWEVER, they **cant identify which SNP or gene** is causal as many SNPs are often co-inherited together - more correct to refer to an **associated locus** than to a specific SNP or gene.

Question 34

what is psoriasis caused by

Answer 34

excessive keratinocyte proliferation, and immune cells activation

Question 35

what is epigenetics?

Answer 35

Epigenetics (=over, beyond genetics) is the study of heritable changes in gene expression **that do not involve changes to the underlying DNA sequence**

Question 36

what is an epigenetic marker

Answer 36

can switch genes on or off

Question 37

what do epigenetic markers affect

Answer 37

DNA or Histones

Question 38

2 types of epigenetic changes involving DNA and histones

Answer 38

cytosine methylation or histone methylation or acetylation

Question 39

what is functional genomics?

Answer 39

attaching FUNCTIONAL information to the DNA sequence transcriptomics, proteomics, and epigenomics is used by functional genomics

Question 40

what kind of disease is fragile X syndrome

Answer 40

genetic mutation in FMR1 is inherited as X-linked dominant

Question 41

fragile x syndrome affects what protein

Answer 41

FMR1

Question 42

how many repeats does one have in fragile X syndrome? what happens when an individual has these repeats

Answer 42

**over 200 repeats of the trinucleotide CGG in FMR1**, while normal people have 6 to 50 repeats. Too many CGGs cause the CpG islands at the promoter region of the FMR1 gene to become hypermethylated Hypermethylation turns the gene off, stopping the FMR1 gene from producing fragile X mental retardation protein 1. Loss of this specific protein causes a build-up of toxic proteins and fragile X syndrome.