POM 16 - Introduction to medical genetics and mendelian inheritance

Question 1

what is RNA

Answer 1

single strand molecule that is transcribed from DNA and translated into proteins by ribosomes

Question 2

what are the 4 categories of genetically determined diseases

Answer 2

single gene disorders

chromosomal disorders

multifactorial disorders

somatic cell disorders

Question 3

what are mutations

Answer 3

permanent heritable change in the sequence of genomic DNA

change in DNA from its natural state which may be disease causing or benign normal variant

Question 4

what is polymorphism

Answer 4

occurrence of 2+ alternative genotypes which each at a frequency greater than that which would be maintained by recurrent mutations alone

natural variations in genomic DNA sequence which have no obvious adverse effects on individual and occur with high frequency

Question 5

why are polymorphisms important

Answer 5

evolutionary advantage to have variety

Question 6

what are the 6 types of mutations

Answer 6

silent

missense

nonsense

frameshift

splice donor/acceptor

InDel

Question 7

what is a silent mutation

Answer 7

single base change in protein coding part of DNA that does not result in an amino acid change

Question 8

what is a missense mutation

Answer 8

single base change that does result in amino acid change but may not cause an abnormal phenotype

Question 9

what is a nonsense mutation

Answer 9

single base change that changes an amino acid to a STOP codon and truncates the protein that is made

Question 10

what is a frameshift mutation

Answer 10

insertion/deletion of bases in anything other than a multiple of 3 and changes the reading frame

Question 11

what is a splice donor/acceptor mutation

Answer 11

alteration of sequences for accurate splicing of introns

Question 12

what is an InDel mutation

Answer 12

a frame shift mutation

insertion/deletion of one or more bases - if its not a multiple of 3 bases then will shfit reading frame

Question 13

what are the 2 strands of DNA called

RNA is a transcribed version that is complementary to what strand of DNA

Answer 13

sense and antisense strands

RNA is complementary to the sense strand - looks like the antisense strand of DNA

Question 14

what eventually happens in a frameshift mutation

Answer 14

eventually introduces a stop codon by random chance in frameshift mutation

Question 15

what is nonsense mediated decay

Answer 15

if peptide produced is going to be nonsense then the RNA encoding it is often broken down/decayed

Question 16

what is a somatic genetic mutation and who can it affect

Answer 16

if a new mutation occurs in the non gamete forming cells

consequences of mutation are limited to the person in whom the changes occurred

Question 17

what is a germline genetic mutation and who can it affect

Answer 17

new mutation occurs in cells that form gametes

change my be transmitted to and inherited by subsequent generations

Question 18

how many pairs of chromosomes do humans have and which are sex chromosome

Answer 18

23 pairs

one pair of sex chromosomes and 22 pairs of autosomes

Question 19

where do genes occupy

Answer 19

specific loci/positions on chromosomes

Question 20

what does it mean to say genes are paired

Answer 20

one paternal one maternal

Question 21

what are alleles

Answer 21

alternate forms of genes

Question 22

what does homozygous and heterozygous mean

Answer 22

if the maternal and paternal alleles are identical = homozygous

if the maternal and paternal alleles differ = heterozygous

Question 23

what are the 2 phenotypic consequences of mutations

Answer 23

gain of function mutations

loss of function mutations

Question 24

what is a gain of function mutation

Answer 24

produces either increased amount/activity of the encoded protein/gene product

Question 25

what is a loss of function mutation

Answer 25

produces either reduced amount/activity of the encoded protein/gene product

Question 26

what is the degree of effect that a mutation will have on the phenotype of only one allele is affected

Answer 26

minimal effect as the other allele can still compensate and make the protein

Question 27

what is a null allele

Answer 27

if no functional protein or any protein is produced/results from an allele

Question 28

what is halpoinsufficiency and why might it occur

Answer 28

where one normal allele copy isn’t enough to compensate for the mutated allele

could occur if there is a critical balance between different proteins needed

Question 29

what is a dominant negative effect

Answer 29

the abnormal protein interferes with the protein encoded by the remaining wild type allele

Question 30

what is the proband in a pedigree chart

Answer 30

the individual we are focused on

Question 31

what does dominant and recessive single gene disorders mean

Answer 31

dominant = phenotype of mutation if one allele has been changed by mutation

recessive = phenotype of mutation if both alleles have been changed by mutation

Question 32

if a trait manifests in a heterozygote then is the trait dominant or recessive

Answer 32

dominant

Question 33

what are the 3 types of mendelian patterns of inheritance

Answer 33

autosomal dominant

autosomal recessive

X linked recessive

Question 34

what is the pattern of inheritance for autosomal dominant inheritance - in terms of parents and number of alleles affected

Answer 34

affected person usually has at least one affected parent

only need one of the 2 alleles changed in order to be experiencing the clinical phenotype - the wild type may not be enough for normal cellular function (haploinsufficiency)

Question 35

what is an example of an autosomal dominant inheritance disease

Answer 35

achondroplasia

Question 36

what is achondroplasia in terms of symptoms, inheritance pattern and what gene the mutations affect

Answer 36

autosomal dominant

shortening of proximal limbs, dwarfism via premature ossification of cartilage into bone

mutation in fibroblast growth factor receptor 3 (FGFR3) gene

Question 37

apart from autosomal dominant inheritance how can someone have achondroplasia with two normal parents

Answer 37

spontaneous/de novo mutation in fathers germ cells

Question 38

in achondroplasia cases due to spontaneous father germline mutation what pathways are affected due to FGFR3 mutation and how does this explain why achondroplasia risk increases with paternal age

Answer 38

increased activation of RAS/MAPK and PI3K/AKT pathways

signaling pathways which promote growth and survival of cells are turned on more by FGFR3 mutation so gradually germ cells are selected for better survival so with age you are more likely to fertilize eggs with these sperm

Question 39

what is the pattern of inheritance for autosomal recessive inheritance - in terms of parents

Answer 39

affected people born to unaffected parents

parents are heterozygous asymptomatic carriers

Question 40

when are autosomal recessive disorders expressed phenotypically

Answer 40

phenotype is only expressed in homozygous state - both alleles are mutant

Question 41

what is an example of a autosomal recessive disorder

Answer 41

haemochromatosis

Question 42

what is hereditary haemochromatosis

Answer 42

iron overload over time causes organ and tissue damage and iron deposition

Question 43

what is the concept of locus heterogeneity

Answer 43

multiple genes mutations can lead to same disease

Question 44

what is compound heterozygosity

Answer 44

heterozygous however have both alleles where coding proteins are non functional

Question 45

what is lyonisation

Answer 45

random inactivation of part of one of the X chromosome in femal somatic cells

Question 46

who does X linked recessive inheritance tend to affect in terms of clinical phenotype and what is the pattern of inheritance in terms of the parents

Answer 46

affects mainly males

usually unaffected parents

Question 47

what are the 4 complications to basic mendelian pedigree patterns

Answer 47

pseudo-dominant pattern

variable penetrance

variable expressivity

new mutations/germline mosaicism

Question 48

explain how pseudo-dominant pattern can complicate mendelian pedigree patterns

Answer 48

common recessive disorders can give pseudo dominant pattern

Question 49

explain how variable penetrance can complicate mendelian pedigree patterns

Answer 49

failure of dominant condition to manifest

Question 50

what does penetrance mean in genetics

Answer 50

whether a trait manifests/ is expressed

Question 51

explain how variable expressivity can complicate mendelian pedigree patterns

Answer 51

when clinical phenotype varies between 2 individuals with same genotype even with the same mutation

Question 52

what are the 2 types of genetic heterogeneity

Answer 52

allelic and locus

Question 53

what is allelic heterogeneity

Answer 53

different mutations at the same locus (same gene)

Question 54

what is locus heterogeneity

Answer 54

mutations at different loci

Question 55

what chromosome is affected and how in down syndrome

Answer 55

trisomy 21

Question 56

what causes down syndrome - 2 things

Answer 56

non disjunction during metaphase 1 = 2 paired chromosome copies are not separated properly

translocations = part of chromosome is put on another chromosome

Question 57

describe the mechanisms of translocation

Answer 57

short arm of one chromosome exchanges with the long arm of another chromosome

creates large chromosome and a smaller fragment that often fails to segregate and is lost

Question 58

what are multi-factoral genetic disorders

Answer 58

interaction of multiple genes sequences/polymorphisms/recent mutations with each other and the environment

Question 59

how do somatic cell genetic disorders arise

Answer 59

arise in single cell then propagates - ie not in all body cells and not at all in germ cells

Question 60

are somatic cell genetic disorders inheritable

Answer 60

no