Q2-FUN13/Human Genetic Variability and its Consequences

Question 1

What are the two main types of germline genetic variation?

Answer 1

large scale and small scale

Question 2

what are the 3 main types of large scale germ-line genetic variation?

Answer 2

aneupolidy, translocations/inversion, copy number variants

Question 3

What is aneuploidy?

Answer 3

it is when 1+ individual chromosmes are present in an extra copy or are missing

Question 4

what is a common example of aneuploidy?

Answer 4

trisomy of chromosome 21 (down syndrome)

Question 5

what is the incidence of aneuploidy?

Answer 5

rare (approx 1:1000 newborns)

Question 6

what is the clinical relevance/consequence of aneuploidy?

Answer 6

Usually causes large-scale changes in gene expression with associated clinical consequences (e.g. learning disability, development delay)

Question 7

What are some other less common viable trisomys?

Answer 7

chromosome 13 (patau syndrome)

chromosome 18 (edwards syndrome)

XXY (Kleinefelters)

Question 8

What is a type of viable monosomy?

Answer 8

X - Turner female

Question 9

What is a translocation/inversion?

Answer 9

it is the exchange of DNA during meiosis between 2 different chromosomes

Question 10

what is the incidence of translocatoins/inversions?

Answer 10

approx 1:500 newborns

Question 11

what is the clinical relevance/consequence of translocations/inversions?

Answer 11

there could be a net gain or loss of DNA or a disruption of gene sequence

Question 12

do translocations/inversions have an effect on meiosis?

Answer 12

yes they do

Question 13

What is a large scale copy number variant?

Answer 13

they are deletions or dupllications of DNA of over 1000 base pairs in size. (can go up to many millions)

Question 14

What is the incidence of copy number varients?

Answer 14

we all carry multiple copy number variants in our genome

Question 15

What is the clinical relevance/consequence of copy number variants?

Answer 15

most are benign, but larger ones (over 1M bp) can be pathogenic

the ones over 1M bp cause learning diabilities, autism, epilepsy, etc.

Question 16

what are microsatellites?

Answer 16

they are short (2-5 bp) repeat units in a DNA sequence

Question 17

Where are microsatellites usually found?

Answer 17

most are in the noncoding region

Question 18

What is the incidence of microsatellites?

Answer 18

they are common, we all carry approx 10K microsatellites in our genomes

Question 19

What is the clinical relevance of microsatellites?

Answer 19

they rarely cause diesease, most are benign

Question 20

What is a single nucleotide polymorphism?

Answer 20

it is a single bp change in the DNA. commonly referred to as SNPs

Question 21

What is the incidence of SNP’s?

Answer 21

we all have abt 3.5M SNPs

Question 22

What is the clinical relevance/consequence of SNPs?

Answer 22

most are benign or have a very small effect on disease, but in rare cases they can be strong/disease causing

Question 23

What is an insertion and deletion?

Answer 23

it is a small section of DNA (1-few) that are deleted or added in

Question 24

What is the incidence of insertions or deletions?

Answer 24

we all have approx 20K in our genomes

Question 25

What is the clinical relevance of insertions and deletions?

Answer 25

rarely cause diesease and most are benign, can be damaging if in exons

Question 26

Explain pathogenic mutations?

Answer 26

most mutations are outside of genes (only 2% of the genome is “genic”). so most mutations dont cause disease

Question 27

What are some things pathogenic mutations can do? (5)

Answer 27

Question 28

What can large scale pathogenic variation result in?

Answer 28

significant change in gene expression because proteins levels from different genes can be changed

Question 29

What can small scale pathogenic variation result in?

Answer 29

• Changing of amino-acid sequence (one or more amino acids different)

– Skipping or introduction of an exon (aberrant splicing)

– Premature stop to translation

Question 30

what are the different classes of genetic mutations?

Answer 30

Question 31

Is cancer considered somatic or germ-line?

Answer 31

somatic

Question 32

the accumulation of somatic mutations can lead to _______.

Answer 32

cancer

Question 33

explain why cancer is not a single disease.

Answer 33

• different cancers come from different tissues
• in a cancer, there can be different types of cancer cells
• some cancer cells can be sensitive to one cure but not another cure
• genetic characterization of cancer is a growing field