Intro to clinical genetics Flashcards
karyotyping process
- take a blood sample -> leukocytes (specifically T lymphocytes)
- add mitogen to induce replication and colchicine to degrade spindle fibers (stop division)
- stain chromosomes
p arm
the short arm of a chromosome
q arm
the long arm of a chromosome
chromosome numbering
- 1-22 (23 is x and y) with 1 being the longest and 22 being the shortest
- except they got it wrong initially and 21 is actually a little shorter than 22
chromosomal disorders
- abnormalities in number or structure of chromosome -> too many/few genes or altered genes
- polyploidy and aneuploidy
- insertions, deletions, and tranlocations
single gene disorders
- alterations in coding sequence of a gene produce effects on the function of the protein
- loss (typical), gain, or alteration of function
- single genes are the basis for mendelian inheritance
- autosomal disorders and sex-linked disorders
mitochondrial disorders
- most important function of mitochondria -> production of ATP
- have their own genome
- included in biochemical disorders
- non-mendelian inheritance (maternal inheritance)
multifactorial disorders
•most common genetic disorders and likely the basis for many common diseases
•combination of genes and environment
Contrast with:
•polygenic = many genes acting together
•teratogenic = primarily environmental based
important tool for diagnosing single gene disorders
(autosomal dominant, autosomal recessive, x-linked recessive, x-linked dominant (rare))
•always construct a pedigree
tools for chromosome analysis
- karyotype
- fluorescent in-situ hybridization (FISH)
- comparative genomic hybridization (CGH)
- exome and whole genome sequencing
FISH
- fluorescent in-situ hybridization
- add probe DNA lableled with fluorescent dye
- denature DNA
- if DNA sequence of interest is present, probe will hybridize
CGH
- comparative genomic hybridization
- AKA microarray
- take a well plate and fix an array of DNA fragments from all chromosomes
- patient DNA and control DNA
- yellow color = normal patient DNA
- red color = deletion (control DNA overpowering)
- green color = duplication (patient DNA overpowering)
exome sequencing
- looks at the exons -> determination of the sequence of coding portion of genome
- most mutations that cause disease will likely alter exons
whole genome sequencing
- Expensive!
- sequence introns and exons
- will pick up mutations in promoter regions, introns, and 3’ UTRs
problems with genetic sequencing
- we are all carriers for many diseases
- can detect diseases with future consequences
- sequence variation of unknown clinical significance -> counseling needed
biochemical test for genetic diseasesq
- gas or liquid chromatography
- enzyme assays
- newborn screening
phenylketonuria test
- a simple blood plasma for phenylalanine can diagnose
* loss of phenylalanine hydroxylase (PAH) activity -> accumulation of phenylalanine
Tools for direct DNA mutation analysis
- DNA sequencing
* small DNA probes that hybridize to mutated DNA
linkage analysis
- utilization of trackable gene markers next to the gene of interest
- 23&Me uses this
DNA fingerprinting
- analysis of variation of sequence of human genome to identify individuals
- uses: CSI and paternity
uniparental disomy
both chromosomes of a homologous pair inherited from ONE parent
unstable triplet repeat mutations
developed by the expansion of normally present trinucleotide repeats
presymptomatic genetic testing
- test a person for a genetic mutation that will certainly cause disease later in life
- aka testing for fully penetrant genes
predisposition testing
test a person for a genetic mutation that will possible cause a disease later in life
presymtomatic testing and children
only offered in children when there is a medical benefit, otherwise (ethics) they have to wait until 18 for informed consent
examples of presymptomatic testing in children
- muscular dystrophy
* Cystic fibrosis
examples of presymptomatic testing in adults
- huntington disease
* familial adenomatous polyposis (FAP)
why are predisposition tests problematic
- prediction of disease occurrence is inexact
* they are disorders whose causative gene(s) are incompletely penetrant
how genetic testing differs from other medical testing
- if genetic disease diagnoses, other family members may be at risk (->unique PRIVACY issues)
- if disease is predicted -> potential STIGMATIZATION and DISCRIMINATION
- access to COUNSELING and INFORMED CONSENT prior to test is not widely available
risks of genetic testing (what is counseled)
- could detect false paternity
- stigmatization (ie survivor guilt)
- loss of employment or insurance
- psychological harm
autonomy
- ethical principle
* being free to make decisions
beneficence
- ethical principle
* doing the right thing, promoting well-being, and preventing harm
nonmaleficence
- ethical principle
* doing no harm
justice
- ethical principle
* being fair
veracity
- ethical principle
* telling the truth
fidelity
- ethical principle
* keeping all contracts and promises
chemical individuality
every individual has his/her own unique constitution of gene products, produced in response to the combined inputs of the genome sequence and one’s particular environmental exposures and experience
