Term
|
Definition
| cells need to be undergoing mitosis/meiosis |
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|
Term
| Levels of DNA packaging during metaphase |
|
Definition
| Double helic, nucleosomes, chromatin, scaffold. loops of chromatin fibers, chromatids |
|
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Term
|
Definition
| Take 0.5ml of blood in culture medium, add phytohaemagglutin, culture for 47 - 72 hrs, add colcemid (arrests cells in metaphase), andd hypotonic KCl, fix in methanol:acetic acid, drop onto slide, digest with trypsin, stain with giemsa |
|
|
Term
| Giemsa binding - what is it used for |
|
Definition
| It produces banding patterns that are chromosome specific. Areas of the chromosome that are gene poor, and heavy in A-T bases stain a darker colour than C-G. Darker bands also tend to be more condensed, and replicate later in S phase than lighter bands. |
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Term
|
Definition
| Chromosomes arranged in order |
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Term
|
Definition
| set of symptoms with a common underlying genetic abnormality - normally changes in chromosome number or deletions |
|
|
Term
| Stages of meiosis 1 and 2. |
|
Definition
1 - prophase 1, metaphase 1, anaphase 1
2 - prophase 2, metaphase 2, anaphase 2 |
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Term
|
Definition
| chromosome line up in middle of cell |
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Term
|
Definition
| spindles attach and crossing over occurs |
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Term
|
Definition
| spindles contract and seperate chromosmoes |
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Term
|
Definition
| nuclear membrane reforms, chromosomes line up again |
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|
Term
|
Definition
|
|
Term
|
Definition
| chromatids are pulled apart once again, four daughter cells, haploid |
|
|
Term
|
Definition
| the structures at which crossing over occcurs |
|
|
Term
| The completion of meiosis II is triggered by |
|
Definition
|
|
Term
|
Definition
| where an organism/cell is missing a few or has a few extra chromosomes |
|
|
Term
| Trisomy is, and is viable on chromosomes... |
|
Definition
| having three copies of a chromosome, 13, 18 and 21 |
|
|
Term
|
Definition
| Downs syndrome, cognitive impairment and characteristic facial appearance, often heart defects and acute leukemia, 10% chance of alzheimers between 40-49 yrs, by 70, it is 100% |
|
|
Term
|
Definition
| Edwards syndrome, 50% of babies die in a month |
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|
Term
|
Definition
| Patau syndrome, most babies die in 6 months |
|
|
Term
|
Definition
| have a single, maternally derived X chromosome, short stature, infertility, normal intelligence, increased risk of organ abnormalities |
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|
Term
|
Definition
| XXY, males who are tall, infertile and have a female distribution of body fat |
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|
Term
|
Definition
| females, mostly undiagnosed |
|
|
Term
|
Definition
| Males, tall, possibly mildly reduced intelligence |
|
|
Term
| Trisomy 21 is normally caused by |
|
Definition
| non-disjunction in 1st meiotic division |
|
|
Term
|
Definition
| failure of the chromosomes to seperate. |
|
|
Term
|
Definition
| a number of clinical syndromes caused by deletions of between 1 and 5 mb, not visible on karyotype, arise due to unequal cross-over events, include DiGeorge syndrome, Williams syndrome, angelamn and Prader-Willi syndromes |
|
|
Term
| Contiguous gene deletion syndromes |
|
Definition
|
|
Term
|
Definition
| deletion of part of 22q11, causes ventricular septal defect (heart murmur), slow mental development, distinctive facial structure, weak immune system, normally new mutation |
|
|
Term
| Fluorescent in situ Hybridisation (FISH) how it works |
|
Definition
| clone DNA and label with biotin before denaturing. denature a seperate chromosome. Allow to hybridise, then use fluorescent antibodies against biotin to show where the probe DNA is on the chromosome |
|
|
Term
|
Definition
| caused by a 1.4Mb microdeletion, aortic stenosis, hypercalcaemia, mild mental retardation, elfin face, behavioural abnormalities, good verbal skills, poor spatial |
|
|
Term
| Meiosis in males and females. |
|
Definition
| Males it begins in puberty, females at birth. |
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|
Term
|
Definition
| index case: the affected individual through whom a family comes to the attention of the investigator |
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|
Term
|
Definition
|
|
Term
|
Definition
| The person presenting for genetic advice |
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|
Term
| Pedigree symbols for dead, male, female and twins and sex unknown |
|
Definition
| Dead, line through diagonally, male is a square, female circle, twins are two line originating from the same point, sex unknown is a diamond |
|
|
Term
| Dominance and recessiveness are properties of... not ... |
|
Definition
|
|
Term
| A character is dominant if... and recessive if not |
|
Definition
| present in a heterozygote |
|
|
Term
| Mendelian patterns of inheritance |
|
Definition
5 in total
Autosomal Dominant/Recessive
X-linked Dominant/recessive
Y linked |
|
|
Term
|
Definition
| Manifests in heterozygotes, transmitted generation to generation, male and female does not matter. Can normally be traceable, 50% of children with one affected parent have it. |
|
|
Term
|
Definition
| Only affect homozygotes, hard to trace through family tree, affects males and females equally, 1/4 chance for a child with a single affected parent to have it, often found in consanguineous relationships |
|
|
Term
|
Definition
| mutations in the same gene produce two or more different conditions |
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|
Term
|
Definition
| Traits only show in males , diagonal transmission, males transmit to carrier daughters, females have a 50% chance to pass to males |
|
|
Term
|
Definition
| Males and females affected, but females more likely, but will be less severe, affected males transmit to all daughters, affected females transmit to daughters and sons. Child of an affected female has a 50% chance of being affected |
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|
Term
|
Definition
| affects only males, males always pass to sons unless novel mutation |
|
|
Term
|
Definition
| expansion of triplet repeats causes severity to increase with each generation |
|
|
Term
|
Definition
| An individual with two or more different cell lines from one zygote |
|
|
Term
|
Definition
| An individual inherits both chromosomes of a homologous pair from the same parent |
|
|
Term
|
Definition
| A gene or region of a chromosome shows different expression depending on the parent of origin |
|
|
Term
| Mitochondrial inheritance |
|
Definition
| Maternally inherited, but affects both sexes |
|
|
Term
|
Definition
| multiple effects of a gene |
|
|
Term
|
Definition
| Variation in phenotype from person to person |
|
|
Term
|
Definition
| The proportion of heterosygotes for a dominant gene that express a trait, even if mildly |
|
|
Term
|
Definition
| Some heterozygotes for a dominant mutation show no symptoms |
|
|
Term
|
Definition
| Deletions, Insertions, Missense, Nonsense, Splice Site, Frame shift, and dynamic |
|
|
Term
| What must be true for hardy-weinberg? |
|
Definition
| random mating,no migration, genetic drift, or natural selection, a reasonably sized population |
|
|
Term
|
Definition
|
|
Term
| What are somatic cell hybrids |
|
Definition
| human cells fused with rodent cells, which lose chromosomes, preferentially human ones, until a stable line exists, which is mostly rodent |
|
|
Term
| The most useful somatic cell hybrids are |
|
Definition
| ones with only one human chromosome |
|
|
Term
| What is mendel's second law, and what is the exception to it? |
|
Definition
| Alleles at different loci segregate independently, linkage, as alleles at linked loci co-segregate |
|
|
Term
| Linkage can be used to create |
|
Definition
| maps, based on marker to disease, or marker to marker linkage |
|
|
Term
| Crossovers to create genetic maps |
|
Definition
| Linked loci will co-segregate unless seperated by a crossover, the closer the two genes are the less likely a crossover is. Crossover can be detected in offspring and this shows how close the genes are |
|
|
Term
|
Definition
| the frequency at which a recombination event occurs between two genes. Normally number of recombinant children in a generation - averaged over many generations |
|
|
Term
| Two unlinked loci have a recombination fraction of |
|
Definition
|
|
Term
|
Definition
| (z) a measure of the likelihood of genetic linkage between loci |
|
|
Term
| A negative LOD score means |
|
Definition
| linkage is less likely than independent assortment |
|
|
Term
| To work out the odds for LOD scores |
|
Definition
probability of segregation at 0
-------------------------------
probability of segregation observed at 0 = 1/2
When 0 = recombination fraction |
|
|
Term
| If there is complete linkage, the recombination is |
|
Definition
|
|
Term
| IN linkage nucleotides which three polymorphisms are used to make maps |
|
Definition
| SNPs, microsatellites, restriction fragment length polymorphism |
|
|
Term
| A variant with a frequency of above 0.01 |
|
Definition
|
|
Term
| A variant with a frequency below 0.01 |
|
Definition
|
|
Term
| DNA change that occurs during germ cell formation |
|
Definition
|
|
Term
| Why does a copy number change in a single gene make a difference, and give an example |
|
Definition
| haploinsufficiency, alphaglobin has two copies and an inactive pseudo gene, and beta globin has one gene Loss of one copy of either results in beta/alpha-thalassaemia, respectively |
|
|
Term
|
Definition
| chromosomes break and rearrrange |
|
|
Term
| Nonsense mutations occur when |
|
Definition
| small indels that are not multiples of 3 occur |
|
|
Term
|
Definition
| the result of a nonsense mutation, the mRNA is unstable and degrades rapidly |
|
|
Term
| Why might a small group of congenital disorders that do not have a high mutation rate appear at high frequency in children born to older fathers? |
|
Definition
| The mutations that cause them give a growth advantage to the sperm progenitors e.g. Achondroplasia |
|
|
Term
| FGFR mutations often produce |
|
Definition
|
|
Term
|
Definition
| particular combination of alleles along a chromosome |
|
|
Term
| How large is the human genome>? |
|
Definition
|
|
Term
| Charcot Marie Tooth disease |
|
Definition
| Abnormalities in myelination, foot deformity, 17p, either 1.5Mb duplication in PMP22, or missense mutation in same gene. |
|
|
Term
|
Definition
| Distinctive facial appearance, cardiac anomalies, skeletal abnormalities, immune defects, mild to moderate retardation, only around 400 cases reported, caused by mutations in ML22 |
|
|
Term
|
Definition
| Presence of more than one type of organellar (mitochondrial or plastid) DNA within a cell/individual |
|
|
Term
| Leber heriditary optic neuropathy |
|
Definition
| Eye issue, G to A substitution at ND4 |
|
|
Term
|
Definition
| DNA change that will pass to the daughter cell, but does not depend on sequence changes |
|
|
Term
|
Definition
| Methyl groups are attached to cytosine by DNA methylases to prevent the gene being transcribed |
|
|
Term
|
Definition
|
|
Term
| What happens to DNA methylation in the embryo |
|
Definition
| Almost all of the methylation is erased and re-established |
|
|
Term
|
Definition
| The dense body that forms after one X chromosome is inactivated by being methylated |
|
|
Term
| What does the XIST gene do and how? |
|
Definition
| Inactivates one X chromosome by producing an RNA that coats the chromosome that produces it. XIST is only active in cells with two X chromosomes. Only expressed from the inactive chromosome |
|
|
Term
| Are both paternal and maternal alleles of an autosomal gene expressed? Yes, in all but 100 genes |
|
Definition
| Yes, in all but 100 genes, in those genes an imprint marks if it is paternal or maternal, and one of the alleles is silenced |
|
|
Term
|
Definition
| Adds ubiquitin to a wide range of proteins, marking them for degredation, expressed only from maternal allele |
|
|
Term
|
Definition
| short, repeated DNA sequences (arrays), often triplet repeat, cause disease when array expands enough |
|
|
Term
|
Definition
| X-linked most common cause of mental retardation, behavioural disorders, twice as common in men than women, and more severe, caused by a dynamic triplet repeatin the FMR1 gene that triggers methylating and silencing of the promoter |
|
|
Term
|
Definition
| Most common inherited ataxia, autosomal recessive, caused by a triplet repeat expansion in the intron of the FRDA gene, loss of FRDA damages mitochondria and leads to iron build up and free radicals |
|
|
Term
|
Definition
| Dominant inheritance, with anticipation, congenital, extending triplet repeat in DM1 |
|
|
Term
| Polyglutamine tract diseases- how many are there, what sort of mutation causes them, what symptoms do they all lead too and why? |
|
Definition
| Nine, expanding CAG repeat, late onset neurodegenerative disease, because the polyglutamine tract in the protein is toxic to neurons |
|
|
Term
| In the UK, what is used to determine if a woman is offered an invasive prenatal test? |
|
Definition
| Maternal age, ultrasound, biochemical markers in maternal serum |
|
|
Term
| What is preimplantation genetic diagnosis |
|
Definition
| It is offered if there us a previous history of a genetic disorder, as it is invasive and has a risk of miscarriage. It is used to test for presence of a Y chromosome if risk of an X linked disorder, and tests for RhD gene in women who are RhD negative, uses PCR |
|
|
Term
| Diagnosis of large deletion usually requires |
|
Definition
|
|
Term
| What is comparative genomic hybridisation? |
|
Definition
| It uses a molecular techniqueto measure DNA copy across the genomes, can identify gains and lossses not visible from karyotyping, compares a standard genome with the patients by labelling both fluorescently, and comparing the colour ratio |
|
|
Term
| What is Quantitative PCCR |
|
Definition
| PCR used under conditions where the amount of product is proportional to the amount of template, so reflects the number of genome copies |
|
|
Term
| What is quantitative fluorescent PCR |
|
Definition
| Quantitative PCR that is used to test for trisomies |
|
|
Term
| How is huntingtons detected? |
|
Definition
| Triplet repeat expansions are identified via PCR followed by gel electrophoresis |
|
|
Term
| How is myotonic dystrophy detected? |
|
Definition
| Southern blotting/ gel electrophoresis, if the triplet repeats are present a smear occurs instead of a band |
|
|
Term
| How is fragile X syndrome detected |
|
Definition
|
|
Term
|
Definition
| requires knowledge of the exact mutation, useful where frequency of a particular mutation is high, often used for sickle cell, thalassaemia and tay-sachs |
|
|
Term
|
Definition
| Result of a pGlu6Val mutation in beta globin, red cells distorted, clump together using vascular ischemia, heterozygotes have increased resistance to malaria, which increases frequency in certain populations |
|
|
Term
|
Definition
| A rare and normally fatal recessive disorder that causes weakness, loss of vision and hearing, and seizures, most children die before 4 years, loss of an enzyme causes a build up of a ganglioside, 10x more common in askenazi jews than the rest of the popultion |
|
|
Term
| Why is whole genome sequencing rarely used as a diagonostic tool? |
|
Definition
|
|
Term
| Cystic fibrosis inheritance pattern |
|
Definition
| autosomal recessive inheritance |
|
|
Term
|
Definition
| Pulmonery disease, exocrine insufficiency, hepatic disease, intestinal abnormalities, increase in sweat electrolytes, infertility, male urogenital abnormalities, obstructive azoospermia |
|
|
Term
| Life expectancy for Cystic fibrosis patients |
|
Definition
|
|
Term
| Mutated gene in cystic fibrosis |
|
Definition
| 3bp deletion in gene for CFTR, causes loss of phenylalanine, a deltaF508 mutation |
|
|
Term
| What causes mucus build up in cystic fibrosis patients |
|
Definition
| defective Cl- secretion and NA+ hyperabsorption deplete airway surface fluid, leading to a build up of mucus |
|
|
Term
|
Definition
| Infection -> Inflammation -> Tissue damage |
|
|
Term
| Cystic fibrosis molecular pathway |
|
Definition
| mutant CFTR retained in ER and degraded, patients homozygous tend to be more severly affected |
|
|
Term
| Amplification refractory mutation system |
|
Definition
| A form of allele specific PCR often used in CF diagnosis, uses allele specific primers, two PCR reactions are carried out in parralel, for each one primer is common, in one PCR the other primer attaches to wthe wild type and the other to the muation, follow with electrophoresis |
|
|
Term
| How do mendelian diseases persist in human populations |
|
Definition
| High muation rate, sperm selection, heterozygote advantage, onset of symptoms after reproductive age. |
|
|
Term
|
Definition
| (PKU), metabolic disorder,all newborns in uk screened, caused by a deficiency in PAH, treatable by a low protein diet and supplements |
|
|
Term
| Newborn blot screening for phenylketonuria |
|
Definition
| requires measuring the levels of phenylalanine with a mass spectrometer |
|
|
Term
| MCADD- medium chain acyl-CoA dehydrogenase deficiency |
|
Definition
| Build up of medium-chain fatty acids, especially during sickness or fasting, leads to hypoglyceamia, seizures, brain damage and death |
|
|
Term
|
Definition
| Mass spectroscopy for fatty acids |
|
|
Term
| Duchenne muscular dystrophy symptoms |
|
Definition
| Muscle weakness that is progressive and symmetrical, abnormal muscle biopsy, often cardiomyopathy and mental impairments are present |
|
|
Term
|
Definition
| signs of DMD are not apparent until several years after birth, gowers noticed a distinctive way in which patients raised themselves off the groumd |
|
|
Term
| How is duchenne muscular dystrophy inherited? |
|
Definition
|
|
Term
| The gene that mutated in duchenne muscular dystrophy is on |
|
Definition
|
|
Term
| Why are a few females affected by Duchenne muscular dystrophy |
|
Definition
| preferential inactivation of X chromosome |
|
|
Term
| The largest human gene is |
|
Definition
|
|
Term
| Difference between becker and duchenne muscular dystrophy |
|
Definition
| In DMD no/little dystrophin, BMD, abnormal, normally shortened protein, caused by indel rather than reading frame shift |
|
|
Term
|
Definition
| Anchors the muscle cell to the extracellular matrix |
|
|
Term
| Cancer grows througha series of |
|
Definition
|
|
Term
|
Definition
| Benign tumour, over proliferation of cells that otherwise appears normal |
|
|
Term
|
Definition
| Benign tumour, normal in appearance but in the wrong place |
|
|
Term
|
Definition
| cells that appear abnormal, often increased nuclear to cytoplasmic ratio |
|
|
Term
|
Definition
| Large growth of a dysplastic cell |
|
|
Term
|
Definition
Proliferation: grow independently of signals
Avoidance of cell death: apoptosis, they don’t do it
Immortality: avoid telomere shortening
Angiogenesis: they must be fed
Metastasis: many activities need |
|
|
Term
| What types of mutations cause cancer? |
|
Definition
| Gain of function in proto-oncogenes, loss of function in tumour suppressor genes |
|
|
Term
| Retinoblastoma inheritance pattern |
|
Definition
|
|
Term
| Li-Fraumeni syndrome, inheritance and effects |
|
Definition
| autosomal dominant, makes patient more susceptible to cancers |
|
|
Term
|
Definition
| protein that triggers apoptosis if DNA synthesis fails |
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|
