Genetic Contributions to Common Disease Flashcards
What is genetic drift?
variation in the relative frequency of different genotypes in a small population
- due to the chance disappearance of particular genes as individuals die or do not reproduce
- REDUCE GENETIC DIVERSITY
Why is loosing alleles in a population due to genetic drift bad?
-at first, those alleles may not have a huge role, but if an old pathogen is RE-INTRODUCED, that the allele had previously protected for, now you have a population at risk for wipe out due to lacking the protective allele.
Individual vs. population when it comes to protective allele loss?
- in a population, some members will lack a protective allele for certain pathogens due to genetic diversity. BUT herd immunity will protect them, the disease won’t be as widespread or endemic
- also individual death is not as traumatic as pop death
what is herd immunity?
- when individuals are protected by the resistance of the population to a certain disease or pathogen
Generally speaking why is loosing genetic diversity bad?
- because genetic diversity incase population’s ability to fight new/ recurrent diseases
- no genetic diversity= one bad pathogen could potentially wipe out entire population
What is Hybrid Vigor?
-populations with more allelic diversity will outgrown/outbreed the populations with less allelic diversity since diversity leads to increased resistance to pathogen & better adaptability to env changes
Different types of mutations and their consequences?
- phenotypes (severity of disease) depends on whichmuatted alleles person gets and where those alleles have mutations
- can be at any point of DNA synthesis, repair, trxn, translation, splicing UTR region; ANYWHERE ON THE GENE
Chromosomal disorder and their affect on pregnancy?
- many chromosomal disorders are too severe to survive
- 50% of first trimester miscarriages, 5% still births
How can we tell WHEN the chromosomal abnormality occurred?
- if in 100% of individuals cells, came from the parents germ cells (meiosis)
- if only in a small subset of cells, then could have occurred anytime after fertilization (mitosis)
What is it called when have 3 of each chromosome in genome?
Triploidy= 3 complete copies of the genome
What is it called when have 3 chromosomes at ONE location in a genome?
-trisomy (most common chromosome abnormality)
Numerical chromosome abnormalities? Structural abnormalities?
1) Euploid or Aneuploid
2) deletions, duplications, translocations, inversions rings
What is euploid? Aneuploid?
1) multiple number of haploid number (N)
- triploid, diploid, tetraploid
2) unbalanced number of chromosomes (too many/few)
- trisomy, monosomy
Most common chromosomal abnormality?
-Trisomy (Down syndrome, Trisomy 21)
What is nondisjunction? When can it occur?
- the failure of one or more pairs of homologous chromosomes or sister chromatids to separate normally during meiosis
- occur in meiosis 1 OR 2
- can lead to trisomy or monosomy
What happens during nondisjunction in meiosis 1?
- the tetrad (duplicated mom & dad chromosomes) are not evenly separated into daughter cells
- have one cell w/ both mom &dad; one daughter cell with ZERO genetic material
What happens during nondisjunction in meiosis 2?
- the sister chromatids fail to separate into distinct daughter cells
- one cell gets, BOTH sets of chromosomes from mom/dad, other daughter cell gets none
Is nondisjunction occurring with all the chromosomes?
- No. This is just a single chromosome, the rest of chromosomes may separate equally & correctly.
- each chromosome separates independently, not reliant on what the number chromosomes are doing
If took genotype of trisomic kid, can you see where the nondisjunction occurred?
Yes. Because each grandparent tparent has a unique genotype. Will be able to see if they have chromosomes from ONLY one grandparent (meiosis 2) or from BOTH grandparents (meiosis 1)
Which parent is usually the problem w/ nondisjunction? Why?
- typically the mother, risk is proportional to mothers age
- because women are doing meiosis every month at ovulation until menopause
- means eggs are more likely to have disfunction in meiosis than sperm which undergo mitosis
Female reproduction outline?
- start meiosis 1 at 20 weeks fetal
- arrest in prophase until puberty, then complete meiosis 1 every ovulation
- complete meiosis 2 upon fertilization w/ sperm
- therefore cells are arrested & performing meiosis throughout women’s fertile life
1) chromosomal deletions
2) chromosomal duplications
1) a portion of the chromosome is missing/deleted
2) a portion of the chromosome is duplicated creating extra genomic material
chromosomal translocations? The two types? Why are they so bad?
- when a portion of one chromosome is transferred to another chromosome
1) robertsonian translocation
2) reciprocal translocation- BOTH can lead to balanced/unbalanced*
-are bad when have an unbalanced translocation and are missing segments of genetic material
What is a Robertsonian translocation?
- when an entire chromosome gets placed on top of another chromosome at the centromere (usually head-head)
- usually attaches to the p arm
- can be balanced or unbalanced
What are chromosomal inversions?
when a portion of the chromosome has broken off, turned upside down, and reattached
-genetic material is now inverted
What are chromosomal rings?
- a portion of a chromosome has broken off and formed a circle or ring
- this can happen with/without loss of genetic material
What are isochromosomes?
-chromosomes supposed to split down the middle, but instead they separated
effect of meiotic recombination on homologous chromosomes?
- can be balanced, when no genetic material is lost (usually symptomless) or unbalanced (devastating)
- leads to patchwork inheritance due to crossing over between homologous chromosomes
- occurs during meiosis , increases genetic diversity & heterogeneity
What is an unbalanced translocation?
- when a parent had a translation as a result of their parents egg+ sperm combo
- parent has equal amount fo genetic material none is missing
- when have child though, can pass on extended chromosomes or nearly deleted chromosomes therefore creating an imbalance and a gain/loss of genetic material (monosomy or trisomy) which leads to genetic disorders
What is an unbalanced translocation?
- when a parent had a translation as a result of their parents egg+ sperm combo
- parent has equal amount fo genetic material none is missing
- when have child though, can pass on extended chromosomes or nearly deleted chromosomes therefore creating an imbalance and a gain/loss of genetic material (monosomy or trisomy) which leads to genetic disorders
How use FISH to detect chromosomal abnormalities?
- we can paint chromosomes unique colors and see them in interphase or metaphase
- see if all chromosomes are present (2 of each color) and see if they are translocated onto other chromosomes or not
Different kind of FISH techniques?
1) entire chromosome
2) locus specific (with DNA specific fluorescent probe)
3) centromere repeat probe
1) 3q29 mean?
chromosome 3, q arm, band 29
What is anticipation mean?
- involved in alzeihmers & other disorders
- means that each generation has a higher risk of having more severe disease since triplet repeats increase with each generation
- saying symptom gets worse with each generation
CAG repeats in healthy person? CAG repeats for Alzeihmers? reduced penetrance range?
1) 1-34 you are healthy
2) 35-39 decreased penetrance, have a range
3) 40 and above have disease
- more repeats you have is correlated to earlier onset of disease symptoms
