Genetics Flashcards

Question

What is a Reciprical Translocation?

Answer 1

Material exchange between homologous chromosomes

Answer 2

Often no effect Can produce offspring with unbalanced chromosomal complement Can give partial trisomy or monosomy

Answer 3

Mental retardation

Answer 4

``` XO females Sterile Short stature Webbed neck Only monosomy compatible with development ```

Answer 5

2-10 copies circular DNA

Answer 6

Maternally

Answer 7

Mutation in some mitochondrial DNA Affects how strong phenotype is Can pass to some offspring but not others Severity of disease can change over time

Answer 8

``` Leber's hereditary optic neuropathy Mitochondrial mutation Mutation in NADH dehydrogenase Optic nerve damage Blindness ```

Answer 9

Mitochondrial mutation Mutation in ATP Synthase Degeneration of basal ganglia Problem with nervous system

Answer 10

Mitochondrial mutation Deletion of mitochondrial DNA Bone marrow failure Problem with immune system and blood

Answer 11

Defects in a single gene | Simple, Mendelian patterns of inheritance

Answer 12

Chance of inheriting disease if carrying the mutation Genetic background determines if you have mutation Some diseases can be decreased with changing diet and environment

Answer 13

Variation in phenotype in affected individuals due to genetic background

Answer 14

Expression of alleles depends on which parent they are inherited from Only affects minority of genes

Answer 15

Prader-Willi syndrome Angelman syndrome Beckwith-Wiedemann syndrome

Answer 16

Allele and genotype frequencies remain the same unless specific disturbing influences are introduced

Answer 17

``` Non-random mating Mutations Selection Random genetic drift Gene flow ```

Answer 18

P+q=1 p2+q2+2pq=1 Homozygous AA=p2 aa=q2 Heterozygous Aa=2pq

Answer 19

``` Disease Map position of gene Gene Gene product Functional studies From genotype to phenotype ```

Answer 20

Based on genetic distance Find genetic marker coinherited with disease Markers 10^6 apart have 1% recombination frequency meaning they are likely to be coinherited Polymorphic markers vary person-person and chromosome-chromosome Measure linkage by LOD score...>3 indicates linkage

Answer 21

Restriction fragment length polymorphisms Polymorphic marker Single base changes - gain/loss or restriction site

Answer 22

Variable number tandem repeats Polymorphic markers 20-30bp repeats

Answer 23

Used in fingerprinting | Di, tri, tetra nucleotide repeats

Answer 24

Single base changes occur every 300bp | Linkage analysis

Answer 25

Regional genetic map Markers to select genetic clones Produce a contig

Answer 26

Overlapping fragments of cloned DNA representing the entire region

Answer 27

``` Screen cDNA libraries Search for CPG Islands Zoo blotting Exon trapping CDNA selection ```

Answer 28

``` Genetic maps available Thousands mapped genes and Expressed Sequenced Tags Genes predicted from genomic sequence Rapid identification of candidate genes Computers used ```

Answer 29

``` Chronic lung disease Bowel obstruction Pancreatic failure Increased sweat electrolytes Premature death ```

Answer 30

RFLP linkage on 7q31 MET is a target kinase receptor, it is close to CF gene but need even closer marker Chromosome jumping and walking

Answer 31

250kb 27 exons 6.5kb mRNA 1480 amino acids

Answer 32

Cystic fibrosis transmembrane conductance regulator Transmembrane protein ATP binding site Chloride channel when fails increases salt conc making thicker mucus

Answer 33

Mainly phenylalanine deletion

Answer 34

Cell culture studies to create transport defects | Knockout mice to develop correct pathology to disease when exposed

Answer 35

X-linked recessive 1:4000 boys Death before 30 chromosome translocations through Xp21 in girls, deletion in boys

Answer 36

Xp21 probes - one loosely linked marker Cloned Xp21 translocation - tightly linked marker Subtractive cloning using Xp21 deletions to mark out what was missing - close marker

Answer 37

``` 2000kb >65 exons 16kb mRNA 368 amino acids Mutations common ```

Answer 38

Dystrophin 427kb Features in common with muscle structural proteins 0.002% muscle protein Links actin to protein complex in plasma membrane Links muscle cells to basal lamina

Answer 39

``` Large deletions (highly truncated protein) causes severe disease Small deletions so only partly truncated causes mild disease ```

Answer 40

Mice have dystrophin deletion didn't show symptoms Eventually diaphragm disintegrated as that muscle worked the most Failure of repair so degradation

Answer 41

Autosomal dominant Progressive neurodegeneration Late onset First disease to be mapped by linkage 1983

Answer 42

Normal 16-36 repeats HD 42-86 repeats First example of trinucleotide repeat expansion

Answer 43

All involve (XYZ)n sequence N is increased All have same markers Severity increases through succeeding generations Can be mitosis/meiotically unstable - increase expansions

Answer 44

(CGG) >200 | Increase methylation so decrease transcription

Answer 45

(CAG) <150 | Multiple effects on protein-protein interactions and toxic protein aggregates

Answer 46

(CTG) 200-400 In 3' untranslated region - direct RNA mediated effects Neuromuscular system affected

Answer 47

(GAA) 200-900 In intron - decreased transcription of Frataxin Affects mitochondrial protein

Answer 48

``` Autosomal recessive Single base change Heterozygous advantage of malaria resistance GAG to GTG beta globin defect Haemoglobin precipitates ```

Answer 49

``` Point mutations Deletions - uneven crossover in meiosis Insertions making stronger globin chains Frame shifts Chain termination to make longer chains Fusion chain where two Hb stick together ```

Answer 50

Single gene disorders Autosomal recessive Decreased synthesis of one or more Hb chains

Answer 51

Alpha0 homozygote - gamma 4 - death

Answer 52

Alpha0/alpha+ compound heterozygote - variable anaemia

Answer 53

Alpha0 heterozygote Alpha0+ homozygote - mild anaemia Alpha0+ heterozygote

Answer 54

Beta0 complete lack of B chains Beta+ decreased B synthesis Not due to deletions Nonsense mutations- premature termination Promoter mutations- decrease transcription Defective splicing- decrease translation

Answer 55

Decreased synthesis of gamma and beta chains Rare Variable anaemia Mild form is hereditary persistence of foetal Hb

Answer 56

Many genes Unclear inheritance Many factors

Answer 57

Interaction between genes acting in a common pathway

Answer 58

Alternate genes in different pathways

Answer 59

All contributing factors in disease termed liability Population shows normal distribution Above threshold disease develops Genetic factors shift curve right increasing chance of disease

Answer 60

Proportion of risk attributable to genetic factors Schizophrenia 81% Type2 diabetes 26%

Answer 61

Not all susceptible individuals affected due to environmental factors Genetic heterogeneity- don't know what genes actually affected as many susceptible Phenocopy - disease purely from environment

Answer 62

Parametric - difficult to apply as assume pattern of inheritance and don't know if dominant or recessive Non-parametric - more successful, do sufferers share common part of DNA that may carry disease gene

Answer 63

Genome wide association studies - SNPs - HapMap to see if inheriting in blocks - thousand genome project

Answer 64

Problems of phenocopy and low penetrance in families Two linkages now refuted Suggest linkage to 6p

Answer 65

Copy number variations at 1q, 15q, 22q 6p-HLA region so perhaps some autoimmune disease 1000s common variants have small effects, difficult to use data

Answer 66

See if individuals inherit same chromosomal region | Whole genome scan to pick out common regions associated with disease

Answer 67

Inherited diabetes in mice | Look for homologous genes in man as genomes very similar

Answer 68

>40 loci identified 6p21 HLA region most important Genetic changes more likely to cause disease Different genes affected in individuals to give a type of diabetes

Answer 69

Linkage analysis unsuccessful as genetically complex Rare inherited forms Many GWAS done as big problem HLA not important - not auto immune disease No main predisposing loci Alleles discovered to increase risk by small a,punt especially if all together but mainly diet

Answer 70

``` Autosomal dominant Monogene disorder Mutation in LDL receptor gene Heart attacks in children 30 loci associated with circulating lipid levels....lipid metabolism important in cardio disease ```

Answer 71

Angiotensin gene causes blood vessel constriction Polymorphism in angiotensin converting enzyme linked to risk of heart attack GWAS 14 loci identified

Answer 72

Autosomal dominant PrPc mutation Could get somatic mutations in gene like cancer

Answer 73

Senile dementia Genetic predisposition Neurofibrillary tangles and amyloid protein plaques which are pathogenic Age related

Answer 74

Plaques from amyloid precursor protein - APP on chr 21 - mutations in early onset families Presenilin 1 on chr14 and presenilin 2 on chr1 - mutations in early onset families Apolipoprotein E on chr19 - lipid transport, late and early onset, 3 major alleles with E4 giving increased risk Epistasis and genetic heterogeneity evident Most late onset no genetic origin

Answer 75

APP into fragments by B secretase Fragments form AB peptide by presenilin Peptide forms plaques with apoliopoproteins Neuronal death

Answer 76

Monogenic defects and Down's syndrome

Answer 77

Remove amniotic fluid and grow foetal cells 16-18 weeks gestation Takes weeks to grow cells Increased miscarriage

Answer 78

Remove part of chorionic villus 11-12 weeks gestation Immediate analysis Sample divides rapidly

Answer 79

Diagnosis and blood screening Heel prick Tests for phenylketonuria as can't break down phenylalanine

Answer 80

Carrier detection Pre-symptomatic diagnosis of late onset disease Eg. Huntington's

Answer 81

PCR based investigations of specific genes Indirect determination DNA sequencing to look for deletions or truncated PCR products Point mutations if there is a known mutation Unknown mutations using screening methods like SSCP and sequencing

Answer 82

Amplification refractory mutation system - PCR primers specific for mutations Loss/gain of restriction enzyme site - can pick up polymorphisms Allele specific oligonucleotides can be hybridised to PCR products Sequencing

Answer 83

Gene not cloned Relies on genetic linkage Allele linkage due to founder effect, polymorphism always associated with mutation Locus linkage- work out linkage of mutant allele to a polymorphic marker in a family, can be unreliable

Answer 84

Physiotherapy and antibiotics for cystic fibrosis | Expands lifespan but doesn't cure

Answer 85

Avoidance of sunlight for xeroderma pigmentosa

Answer 86

Correction of virilisation in girls with congenital adrenal hyperplasia Plastic surgery for Down's- controversial

Answer 87

Restricting phenylalanine intake in patients with phenylketonuria Prevents retardation from build up of metabolites

Answer 88

Insulin for diabetes | Factor VIII administration for haemophiliacs

Answer 89

Natural - heart and lung in CF - bone marrow for thalassaemias to help symptoms Artificial - neoorgans experimental

Answer 90

Pluripotent stem cells - embryonic (ethical) - induced stem cells by putting differentiated cell in mixture of 4 genes Multi potent stem cells- many cell types but not all - mesenchymal stem cells

Answer 91

Correct gene defect with with transgene | Replace gene with homologous recombination- theoretical

Answer 92

Retroviruses, lentiviruses Role to take over cell machinery so efficient Safety problems - must be replication deficient and have insertional mutagenesis

Answer 93

Liposomes Direct DNA injection Receptor mediated endocytosis Can't cross infect so safe

Answer 94

Producing and sustaining high level transgene expression | Foreign gene may be inactivated