Genetics Flashcards
mendelian inheritance and genetic disease, genetic testing (cytogenetics) and multifactorial disorders individuality and personalized medicine
Autosomal Recessive Inheritance chances if both parents Aa
If parents are both carriers of the mutations in the same recessive gene, each pregnancy has :
- 25% chance of inheriting both normal genes
- 50% chance of being a carrier
- 25% chance of inheriting both gene mutations and being affected
= 75 % CHANCES NOT BEING AFFECTED, AND 25% YES
What’s PKU
It is a gene. Mechanism of action: the PAH isn’t working - a disease where phenylalanine can’t be digested (because it can’t be transform to tyrosine since the PAH isn’t working)
allelic heterogeneity
when you have a vast number of different mutation in the same gene that leads to a particular condition
locus heterogeneity
when one disorder is caused by more than 1 gene
Autosomal Dominant Inheritance chances if both parents Aa
Each offsprings of an affected parent has a 75% chance of being affected and a 25% chance of being unaffected
Marfan syndrome
autosomal dominant inheritance - arachnodactyly, lens dislocation, dilation of aorta, arm span that exceeds her height
Pleiotropy
defects in one gene cause multiple clinical manifestations (one gene influences 2 or more seemingly unrelated phenotypic traits)
penetrance
(yes or no). The patient either have the disease or not. Full penetrance = everyone who has the mutation will express the disease in one way or another
expressivity
how a person is affected, what are the symptoms that may differ from one individual from another (like a dimmer switch)
Can the condition of X linked inheritance be transmitted from father to son ?
No, cause he passes his Y chromo
What are the chances of a son being affected if the mother is a carrier in X-linked inheritance ?
Sons of carrier females have a 50% chance of being AFFECTED and a 50% chance of being UNAFFECTED with each pregnancy
What are the chances of a daughter being affected if the mother is a carrier in X-linked inheritance ?
Daughters of carrier females have a 50% chance of being A CARRIER and a 50% chance of being UNAFFECTED with each pregnancy
duchenne muscular dystrophy
- X-linked inheritance
- gowers signs (standing from sitting is difficult)
- caused by a mutation in the DMD gene, one of the largest genes (1/3 mutations occur de novo)
characteristic of Y-linked inheritance ?
never occur in female, and always in males
what is the threshold effect for clinical expression of multifactorial disorders ?
combination of multiple genes (polygenic) and environmental (lifestyle) factors
if one child or parent has a multifactorial disorder, what’s the recurrence risks for the next child ?
5-10%
if more than one child or parent has a multifactorial disorder, what’s the recurrence risks for the next child ?
10-15%
SNPs
- single nucleotide polymorphisms
- an individual’s response to a drug is often linked to these common DNA variations
CNVs
- copy number variants
- disease risk factors in complex disorders (autism)
- change in the number or arrangement of genes
advantages of personalized medicine
- better informed clinical decision
- higher probability of improved health outcomes
- lower probability of adverse reactions from medication
- focus on prevention and prediction of disease
- reduced healthcare costs
most common epigenetics mechanism ?
- methylation of DNA
- modifications of histone proteins
- noncoding RNAs
pharmacogenomics
the study of genetic differences in metabolic pathways that affect individual responses to drugs (high or poor metabolizer)
explain mitosis
- Prophase: The chromosomes condense and the mitotic spindle begins to form.
- Metaphase: The nuclear membrane disintegrate. Each
chromosome is attached at its centromere to microtubules and become aligned along the equatorial plane. They reach maximal condensation. - Anaphase: The centromere of each chromosome divides and the two daughter chromatids separate to opposite poles.
- Telophase: The chromatids have separated and the two groups of daughter chromosomes each become enveloped in a new nuclear membrane.
what’s the p arm ? and the q ?
- p = short arm
- q = long arm
where is the centromere in metacentric chromo ?
medial
where is the centromere in submetacentric chromo ?
distal
where is the centromere in acrocentric chromo ?
near terminal
kinetocore
structure where the spindle microtubules are associated with the centromeric heterochromatin
non-disjunction
2 homologous chromosome or sister chromatids migrate to the same pole as opposed to opposite poles during cell division
constitutional mosaicism
at least 2 cell lines with different chromosomal complement in a fetoplacental unit derived from a single zygote
2 main types of chromosomal abnormalities
- numerical (ex: trisomy)
2. structural (balanced or unbalanced)
the 3 well-defined non-mosaic autosomal chromosome trisomy compatible with postnatal survival ?
- trisomy 21 (down syndrome)
- trisomy 18 (edward syndrome)
- trisomy 13 (Patau syndrome)
what’s the only etiological factor for which a link with aneuploidy is unequivocally recognized in down syndrome ?
advance maternal age
what’s the different of problem on the 21 chromo in down syndrome ?
- 95% free trisomy 21
- 4% robertsonian translocation (14 and 21 chromo)
What are the 3 translocation balanced structural rearrangements?
- RECIPROCAL TRANSLOCATION : deux parties de différents chromo se mélangent
- ROBERTSONIAN TRANSLOCATION : fusion between the long arm of 2 acrocentric chromosomes at their centromeres
- INVERSION: mirror effect of half a chromosome
chromosome banding
voir toute les chromo sur une plaque
chromosome banding advantages
- entire genome view
- can detect balanced and unbalanced rearrangements
limits of chromosome banding
- low resolution
- need an actively growing source of cells
FISH
a DNA probe labeled with a fluorescent dye hybridize directly to the metaphase or interphase chromosome.
benefits of FISH
- higher resolution
- can study non-dividing tissues
limits of FISH
- can only see a part of the genome complementary to your probe
what explains 3/4 cases of XX males with sex reversal ?
SRY gene is translocated on the X chromosome
chromosomal microarray
high resolution genetic test to assess very small gains and losses (copy number variants) of genomic information in an individual.
You hybridize patient DNA with control DNA to their complementary sequences in the array
- green (test DNA) = gain
- red (control DNA) = loss
- yellow = no change
chromosomal microarray benefits
- whole genome approach
- higher resolution than karyotyping
chromosomal microarray limits
- cannot identify translocation or inversions
cause of chronic myelogenous leukemia (CML)
translocation between the 9 and 22 chromo = fusion between BCR gene and the Abelson tyrosine kinase ABL
what are the 2 big reasons for genetic testing ?
- a PREDICTIVE MESURE to screen to carrier status or for something that might happen to you later
- to REFINE A DIAGNOSIS (to figure out which genes are responsable for a disease)
BRCA1 and BRCA genes meaning ?
suseptibility to breast and ovarian cancer (but no complete penetrance)
sanger sequencing
identifying exact sequence changes at individual loci
- PCR-amplified region of interest and read it to compare with normal sequence
panel sequencing
identifying sequence changes in a selected group of genes
exome or genome sequencing
identifying sequence changes in all genes
benefits sanger sequencing
very accurate and established technique, can be used to detect point mutations, small insertions/deletions in known and candidate genes
genetics test seen in class
- karyotyping
- FISH
- microarrays
- sanger sequencing
- panel sequencing
- exome or genome sequencing
what’s the coding portion of the genome ?
the exome, consist of around 1,5-2% of the DNA
illumina sequencing
helps recreate the genome base by base with color associated with nucleotids (used for exome sequencing)
