POM 16 - Introduction to medical genetics and mendelian inheritance Flashcards

1
Q

what is RNA

A

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

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2
Q

what are the 4 categories of genetically determined diseases

A

single gene disorders

chromosomal disorders

multifactorial disorders

somatic cell disorders

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3
Q

what are mutations

A

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

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4
Q

what is polymorphism

A

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

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5
Q

why are polymorphisms important

A

evolutionary advantage to have variety

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6
Q

what are the 6 types of mutations

A

silent

missense

nonsense

frameshift

splice donor/acceptor

InDel

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7
Q

what is a silent mutation

A

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

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8
Q

what is a missense mutation

A

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

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9
Q

what is a nonsense mutation

A

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

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10
Q

what is a frameshift mutation

A

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

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11
Q

what is a splice donor/acceptor mutation

A

alteration of sequences for accurate splicing of introns

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12
Q

what is an InDel mutation

A

a frame shift mutation

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

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13
Q

what are the 2 strands of DNA called

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

A

sense and antisense strands

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

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14
Q

what eventually happens in a frameshift mutation

A

eventually introduces a stop codon by random chance in frameshift mutation

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15
Q

what is nonsense mediated decay

A

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

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16
Q

what is a somatic genetic mutation and who can it affect

A

if a new mutation occurs in the non gamete forming cells

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

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17
Q

what is a germline genetic mutation and who can it affect

A

new mutation occurs in cells that form gametes

change my be transmitted to and inherited by subsequent generations

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18
Q

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

A

23 pairs

one pair of sex chromosomes and 22 pairs of autosomes

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19
Q

where do genes occupy

A

specific loci/positions on chromosomes

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20
Q

what does it mean to say genes are paired

A

one paternal one maternal

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21
Q

what are alleles

A

alternate forms of genes

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22
Q

what does homozygous and heterozygous mean

A

if the maternal and paternal alleles are identical = homozygous

if the maternal and paternal alleles differ = heterozygous

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23
Q

what are the 2 phenotypic consequences of mutations

A

gain of function mutations

loss of function mutations

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24
Q

what is a gain of function mutation

A

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

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25
Q

what is a loss of function mutation

A

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

26
Q

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

A

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

27
Q

what is a null allele

A

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

28
Q

what is halpoinsufficiency and why might it occur

A

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

29
Q

what is a dominant negative effect

A

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

30
Q

what is the proband in a pedigree chart

A

the individual we are focused on

31
Q

what does dominant and recessive single gene disorders mean

A

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

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

32
Q

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

A

dominant

33
Q

what are the 3 types of mendelian patterns of inheritance

A

autosomal dominant

autosomal recessive

X linked recessive

34
Q

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

A

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)

35
Q

what is an example of an autosomal dominant inheritance disease

A

achondroplasia

36
Q

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

A

autosomal dominant

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

mutation in fibroblast growth factor receptor 3 (FGFR3) gene

37
Q

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

A

spontaneous/de novo mutation in fathers germ cells

38
Q

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

A

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

39
Q

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

A

affected people born to unaffected parents

parents are heterozygous asymptomatic carriers

40
Q

when are autosomal recessive disorders expressed phenotypically

A

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

41
Q

what is an example of a autosomal recessive disorder

A

haemochromatosis

42
Q

what is hereditary haemochromatosis

A

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

43
Q

what is the concept of locus heterogeneity

A

multiple genes mutations can lead to same disease

44
Q

what is compound heterozygosity

A

heterozygous however have both alleles where coding proteins are non functional

45
Q

what is lyonisation

A

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

46
Q

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

A

affects mainly males

usually unaffected parents

47
Q

what are the 4 complications to basic mendelian pedigree patterns

A

pseudo-dominant pattern

variable penetrance

variable expressivity

new mutations/germline mosaicism

48
Q

explain how pseudo-dominant pattern can complicate mendelian pedigree patterns

A

common recessive disorders can give pseudo dominant pattern

49
Q

explain how variable penetrance can complicate mendelian pedigree patterns

A

failure of dominant condition to manifest

50
Q

what does penetrance mean in genetics

A

whether a trait manifests/ is expressed

51
Q

explain how variable expressivity can complicate mendelian pedigree patterns

A

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

52
Q

what are the 2 types of genetic heterogeneity

A

allelic and locus

53
Q

what is allelic heterogeneity

A

different mutations at the same locus (same gene)

54
Q

what is locus heterogeneity

A

mutations at different loci

55
Q

what chromosome is affected and how in down syndrome

A

trisomy 21

56
Q

what causes down syndrome - 2 things

A

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

translocations = part of chromosome is put on another chromosome

57
Q

describe the mechanisms of translocation

A

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

58
Q

what are multi-factoral genetic disorders

A

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

59
Q

how do somatic cell genetic disorders arise

A

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

60
Q

are somatic cell genetic disorders inheritable

A

no