Molecular Medicine Flashcards

Question

What are the different CAG repeat sizes of Huntington disease?

Answer 1

Normal- 10-26 Prematuration- 27-41 Affected- 36-121

Answer 2

Neurodegenerative disease Huntington disease aff3cts the part of the brain that controls thinking, emotion, and movement Inability to recognize disgust in others appears in carriers of the Huntington gene before symptoms are manifest Uncontrollable movements, jerky, random, uncontrollable, rapid movement, although some exhibit very slow movement and stiffness, speech like slurring of words

Answer 3

The CAG repeat expansion leads to the production of Huntington protein that contains an abnormal number of glutamines at the N-terminal - This likely disrupts the function of the gene’s protein product, Huntington - the job of its protein product, Huntington, is to direct the delivery of small packages (vesicles containing important molecules) to the outside of the cell - Cellular enzymes cut this elongated protein into fragments that have sticky ends - The protein fragments from abnormal clumps inside nerve cells and may attract other, normal proteins into the clumps These nerve cells don’t function properly

Answer 4

The greater the number of CAG repeats, the earlier the onset of symptoms

Answer 5

Electrophoresis

Answer 6

Medications ease feelings of depression and anxiety; others control involuntary movements Physical or speech therapy helps HD patients lead more normal lives Gene silencing or RNA interference is a promising technique to treat HD

Answer 7

- Affects genes located on the X-chromosome - males are much more likely to be affected because they have only one copy of X-chromosome - Can affect male children of unaffected parents - females are mostly carriers and are unaffected - Sometimes females may show some symptoms of the disease because of X-chromosome inactivation

Answer 8

Frequency- 1 in 10,000 Symptoms: abnormally prolonged bleeding after trauma

Answer 9

1 in 3,000 to 1 in 4,000 Symptoms: muscle wastage in teenage years

Answer 10

Frequency- 1 in 1000 Symptoms- mental retardation

Answer 11

1 in 50,000 to 100,000 births Symptoms,s- recurrent and persistent infections

Answer 12

- caused by a mutation in the SCIDX1 gene located on the X chromosome - This gene encodes a protein that is used to construct a receptor called interleukin-2 receptor, subunit gamma(IL2RG) also called cytokine receptor common gamma chain - Cytokine receptor common gamma chain is found on the surface of immune cells (T cells, natural killer, and B cells) and allow these cells to communicate

Answer 13

The IL2RG receptors cannot form properly or are absent from immune cells As a result, the immune cells can’t communicate with one another about invaders in the environment -Insufficient T and B cells are produced to fight off the infection, and the body is left defenseless

Answer 14

Mutation in IL2RG-receptor gene may be caused by: - missense - nonsense - insertion - deletions, mutations and, - splice defects

Answer 15

Sequence analysis- sequence analysis of the IL2RG coding region Targeted mutation analysis- Southern blot analysis for the detection of large deletions and complex mutations for individuals in whom mutations are not detected by sequence analysis

Answer 16

Alleluia heterogeneity- different mutations within a single gene locus (I.e. multiple alleles of a gene) result in same phenotypic expression. E.g. over 1000 known mutant alleles of the CTFR gene cause cystic fibrosis Locus heterogeneity: variations in completely unrelated gene loci cause a single disorder. E.g. retinis Pigmentosa can have autosomal recessive or X-linked origin

Answer 17

The frequency with which a particular genotype manifests itself in the phenotype- complete or incomplete

Answer 18

Same disease alleles but differences in severity

Answer 19

All body cells aren’t genetically identical

Answer 20

Same symptoms(e.g. deafness) may be caused by an environmental factors (e.g. rubella virus infection) or by an inherited disorder

Answer 21

E.g. phenylketonuria

Answer 22

Severity of disease increases with succeeding generations, e.g. muscular dystrophy

Answer 23

Expression of disease depends on the parent from which it was inherited. E.g. deletion of some genes from chromosome 15: father-Prader-Willi syndrome, mother-Angelman syndrome

Answer 24

Diseases caused by combined effects of multiple genetic and environmental (e.g. age, gender, infection, or nutrition) risk factors) There is no dominance or recessivity at each of these genes - The genes act in concert in an additive fashion, each adding or detracting a small amount from the phenotype - most risk factors probably of small effect individually and with complex interaction

Answer 25

The environment interacts with the genotype to produce the final phenotype Members of the same family are likely to suffer from the same disease - they are likely to share the same environment - They are likely to share the same genes Often not easy to differentiate the relative contribution of genetic and environmental factors in some diseases Genetic tests for predisposition may allow at-risk individuals to change their lifestyle to avoid the disease

Answer 26

- Affected children may have normal parents - Recurrence risk increases with the number of aff3cted children in family - A more severely affected parent is more likely to produce an affected child - Consaguity slightly increases the risk for an affected child

Answer 27

Manic depression Alcoholism Schizophrenia Tourette’s Dyslexia Ahlzeimer’s

Answer 28

Rheumatoid arthritis Various cancers Epilepsy Multiple sclerosis Insulin-dependent diabetes mellitus Non-insulin dependent DM peptic ulcer Ischaemic heart disease Hyperthyroidism Gallstones Migraine Asthma

Answer 29

Neural tube - spina bifida - anencephaly Congenital heart disease Cleft heart disease Mental retardation

Answer 30

Entire chromosomes, or large segments of them, are missing, duplicated, or altered Trisomy Monosomy Translocation: chromosomes break and the fragments rejoin to other chromosomes

Answer 31

45X: turners- 1 in 5000

Answer 32

47XXY :1 in 1000

Answer 33

1 in 800 (maternal age dependent)

Answer 34

1 in 10,000

Answer 35

A number of disorders where there is a decline in energy availability and other clinical abnormalities Mitochondria are maternally inherited, therefore mitochondrial disorders can only be inherited from an individuals mother Different factors lead to great complexity in the age of onset and severity of symptoms Mitochondrial disorders affect many different organs simultaneously, including the central nervous system

Answer 36

The number of mitochondria in a cell depend on the metabolic requirement of that cell Each mitochondria has 2-10 copies of a 16.6 kB circular DNA genome (mtDNA). 90% of cellular energy is generated in the mitochondria by the respiratory chain Mitochondria diseases comprise those disorders that in one way or another affect the function of the mitochondria and/or are due to mitochondrial DNA mutations

Answer 37

Diabetes Some forms of cancer Cardiovascular disease Lactic acidosis Specific forms of myopathy Osteoporosis Ahlzeimer’s Parkinson’s Stroke mtDNA mutations are believed to play a role in aging

Answer 38

CPEO- myopathy and paralysis of eye muscles Affected gene -multiple gene loss because of deletion (results from mitochondria mutation loss)

Answer 39

Symptom- childhood bone marrow dysfunction giving rise to multiple blood disorders and pancreatic failure Affected gene- multiple gene loss because of deletion Mitochondrial mutations

Answer 40

NARP- muscle weakness ataxia and blindness Affected gene- subunits of ATP synthase Mitochondrial mutations

Answer 41

He coined the term DNA fingerprinting: a technique used by scientists to distinguish between individuals of the same species using only samples of their DNA

Answer 42

Subject to interpretation and -valuable samples can be difficult to obtain Uniform nature of DNA in a single individual and the genetic variability between individuals make DNA fingerprinting possible When properly conducted, DNA-based testing not only provides exclusionary evidence, it can provide positive evidence of a person’s identity without bias Forensic scientists scan DNA regions that vary from person to person (VNTR, STR) and use the data to create a DNA profile (DNA fingerprint) of that individual

Answer 43

1. Isolate chromosomal DNA from a sample of cells 2. Cut the DNA with a restriction enzyme 3. Separate the DNA fragments by gel electrophoresis 4. Transfer bands to nitrocellulose 5. Denature the DNA and add probe. Allow probe to hybridize and wash away excess probe 6. Expose the filter to photographic film and compare the results

Answer 44

You look for matches (based on sequence or on numbers of small repeating units of DNA sequence) at a number of different locations on the person’s genome Several matches must be identified to be confident (“beyond a reasonable doubt”) that the right person is identified There is an extremely small chance that another person has the same DNA profile for a particular set of regions

Answer 45

- identify potential suspects whose DNA may match evidence left at crime scenes - exonerate persons wrongly accused of crimes like rape or murder - identify crime and disaster victims - establish paternity and other family relationships - humans, animals, plants (e.g. Cabernet Sauvignon grapes= Cabernet Franc + Sauvignon blanc) Inheritance cas3s Immigration cases Identify endangered and protected species as an aid to wildlife offic8als(could be used for prosecuting poachers) - detect bacteria and other organisms that may pollute air, water, soil, and food - match organ donors with recipients in transplant pr9grams - determine pedigree for plants, seeds, or livestock breeds- e.g. herbal product ginseng - authenticate consumables such as wine

Answer 46

1983-1985: a two year struggle by Chrostiana Sarbah and her son, Andrew, to prove to the home office in England that they were, indeed, mother and son 1986: the Pitchfork murder case- the origins of DNA profiling

Answer 47

The Y-chromosome passed directly from father to son valuable in analysis of: -genetic markers on the Y chromosome is specifically useful for tracing relationships among males -biological evidence involving multiple male contributors

Answer 48

- in the investigation of cases that have not been solved for many years, mtDNA is extremely valuable - Comparing the mtDNA profile of unidentified remains with the profile of a potential maternal relative can be an important technique in missing person investigations Short down 1972 in Vietnam Remains of unknown laid to rest, 1984 Identified and buried 1998

Answer 49

National DNA Dayabase Suspect profiling Database contains DNA profiles of individuals: - suspected of - charged with or - about to be reported for a recordable offense

Answer 50

National DNA indexing system Convicted offender profiling The Combined DNA Index System (CODIS) -uses two indexes: - The Convicted Offender Index contains DNA profiles of individuals convicted of felony sex offenses (and other violent crimes) - the forensic imdex contains DNA profiles developed from crime scene evidence

Answer 51

-many major crimes involves people who also have committed minor offenses - innocent people are often incarcerated for crimes they did not commit - if samples had been taken at the time of arrest, these individuals may have been excluded early in the investigative process - Ability to compare other cases against the arrested person’s DNA profile, just as with fingerprints - Savings in investigation, prosecution, and incarceration. E.g. John Mark Karr/Jon Berret Ramsey case