Gene Inheritance, Meiosis, Cytogenetics Flashcards
what are alleles?
- are different forms of the same gene
- can be multiple, non-identical versions of the gene or only 2 versions depending not the specific gene
- can be dominant or recessive
Alleles and the human genome?
The human genome contains two versions of each gene (a paternal & a maternal copy)
-two copies don’t have to be identical, alleles are the variations in the two genes
Compound Heterozygotes
the presence of two mutant recessive alleles on the same gene locus in a pair of chromosomes
Phenotype of compound heterozygotes?
The symptoms/phenotype may be less severe because each mutant allele may partially complement the deficit of the other mutant allele
-can also be made more severe but this is rare
X-Linked Recessive
- No male–> male transmission since father gives a Y to the son
- Most cases boys
Why X-Linked Recessive Traits Uncommon in girls?
Because having the mutant recessive allele on both X chromosomes usually makes the disease too severe
-often times fatal
How X-Linked Recessive typically passed?
From unaffected carrier female to an affected son
Hypothesis if see only males affected by disease & male–> male transmission?
Autosomal dominant mutant allele but that is turned off/ doesn’t affect women
-due to changes in gene expression in men vs. women
Daughters of a male patient w/ X-linked inheritance and a +/+ female?
All daughters will be carriers
Mutation that causes Hemophilia A?
- X-linked dominant
- more than 2000 sequence variants within the affected gene have been catalogued
X-Linked Dominant Inheritance in females?
- Absence of male–> male transmission because males provide a Y to their sons
- Affected fathers have all affected daughters since donate their mutated dominant X chromosome to their daughter
- Look for affected father, all daughters and no sons affected
What marriage shows a direct difference between X-Linked Dominant and Autosomal Dominant?
Affected father x unaffected mother which gives a unique progeny ratio different than autosomal dominant
X-Linked Dominant Disorder in males?
- if have an affected mother
- some are more severe in males than females causes death during prenatal period
- this can affect the ratio of male:to female affected because all males die before birth
How is mitochondrial genome (mtDNA) inherited?
- Maternally inherited
- Disorders caused by mutations in mtDNA are transmitted from females to all children
Mitochondria & cell division? How does this affect pathogenic nature of mtDNA inheritance?
- each cell has thousands of mitochondria each w/ own mtDNA
- mitochondria are unevenly distributed during cell division
- pathogenic mtDNA mutations can be heteroplasmic
- meaning that an infected women can pass variable amounts of pathogenic mtDNA to child
- meaning child can vary in severity of the disease depending on proportion of pathogenic to healthy mtDNA
Heteroplasmic
Meaning a mix of wild-type & mutated DNA within the same individual
-ex: because each cell has thousands of mitochondria each with own mtDNA, you can have a mix of healthy and pathogenic mtDNA in your body
What is locus heterogeneity? Phenotype of individuals affected?
- when the same disorder can be caused by mutations in different genes
- in some cases phenotype is indistinguishable even when mutation is on different genes
- in other cases phenotypes have clear differences based on the specific mutant gene
What is allelic heterogeneity?
-a disease caused by different mutations in the same gene
-is found in almost all loss of function diseases (ex: hemophilia)
-
Allelic heterogeneity and severity?
- Allelic heterogeneity is when one gene can have multiple mutant alleles
- Severity of the disease phenotype is dependent on which specific mutant alleles the patient has
What is genomic imprinting?
- is when an autosomal gene has only maternally or paternally derived allele active
- the other allele is silenced
Genomic imprinting and diseased offspring?
- If the maternal allele is deactivated in on a specific gene, regardless of whether the allele is mutant or not, the child will be unaffected since that allele is silenced anyway.
- person only affected if the mutant allele is the active allele
What is polymorphism?
Fraction of human genome that is polymorphic?
1) A concept that is explained/defined by genetic diversity
2) 1% level (second most common allele has frequency >/= 1) so a very large fraction of human genome.
What are alternative sequences of the gene called?
Alleles
What does the Hardy-Weinberg law state?
That in the absence of other evolutionary influences (adaptations for survival etc.) , allele and genotype frequencies will remain constant
What does highly polymorphic mean?
That a gene has thousands of alternative versions of alleles for the same gene
-ex: MHC proteins in humans
Homologous recombination in chromosomes
-crossing over between homologous non-sister chromatids (maternal and paternal chromosomes) during cell division can lead to recombinant chromosomes
Effect of homologous recombination?
-the sister chromatids in butterfly shape are no longer identical
When/how are genes linked?
Genes are linked when they are extremely close together on the same chromosome
- closer together the genes, the more closely linked & less likely will be separated by recombination
- means are usually inherited together
How can we determine if two genes are linked?
- their proximity on a chromosome
- and by looking at analysis of recombination with the two genes
Patchwork pattern of inheritance?
Means that during meiosis, we create unique chromosomes through recombination
- is how/ why siblings have different chromosomes
- our chromosomes are “patched together” from crossing over/recombination of parent chromosomes
Twins and patchwork
- identical twins (monozygotic) came from same egg
- crossing over occurs in meiosis, therefore identical twins have same patchwork pattern for any chromosome e
- fraternal twins will have different patchwork patterns for each chromosome since are no different than normal siblings
What are mini satellites?(variable number of tandem repeats)
- polymorphism (variable) reflecting different number of tandem repeats at a specific chromosomal site
- usually 20-70 base pairs repeated
- used in regulating gene expression
- have create different alleles
How detect mini satellites?
-detected by restriction digestion, southern blotting, or hi throughput sequencing
What are micro satellites?
- highly polymorphic simple short nucleotide repeats (di, try, or tetra nucleotide)
- number of repeats is different on different copies of the same chromosome
- used for regulating gene expression
How detect microsatellites?
PCR
What are SNPs? (single nucleotide polymorphism)
- are short insertions of deletions (Indels)
- are polymorphic variations in one base pair in a DNA sequence
How detect SNPs?
Detect by sequence analysis OR allele specific probes
-sequencing is easier since are so small
What are copy number variants (CNV)?
- deletion or duplication of segments of DNA ranging in size from 1kb- several Mb long
- some are common, others very rare
How detect CNVs?
1) array comparatively genomic hybridization (aCGH)
2) other array based methods
How get chromosomes with deletions/duplciations? (CNVs)
-through unequal crossing over during meiosis
indels
short insertion or deletion
IF have four allele variations, how man alleles will an individual person have?
Each person will only have TWO alleles because we are diploid organisms
-we can only have 2 alleles even if have multiple allele Variations
How many sets of chromosomes do we have?
How many chromosomes do we have?
What are the types of chromosomes?
23
46
-22 autosomes, chromosome 23 are the sex chromosomes
12p 12 mean?
Chromosome 12, p arm, band 12
How label individual chromosomes arms?
- short arm=p arm
- long arm= q arm
What are G-bands?
- Giemsa banding
- used in karyotypes
- are numbered in a systematic manner based on position relative to centromere
- as move farther from centromere, numbers get larger
How classify chromosomes?
depends on position of centromere, will either be:
1) metacentric
2) submetacentric
3) afrocentric
Metacentric chromosome?
centromere is in middle, q & p arms are same size
Submetacentric chromosomes?
centromere is closer to one side than other
Acrocentric chromosomes?
centromere is very close to one side
-p arm (upper arm) is extremely short
How many afrocentric chromosomes in human karytotype? What do they encode?
- 5 pairs, or 10 chromosomes
- each pair has genes encoding 18s and 28s rRNA in p arm
Satellite at end of p arm in Acrocentric chromosomes?
p arm= short, upper arm in Acrocentric chromosomes
-is hertochromatic or composed of non-coding DNA
Heterochromatic mean?
Non-coding DNA
What is FISH?
-How does it work?
1) Fluorescence IN SITU Hybridization
2) Attach (hybridize) fluorescence-tagged DNA probe to chromosomes in metaphase, all the chromosomes arestained dull red w/ propidium iodide, then observed in fluorescent light
3) can have multiple colored probes that are chromosome & gene specific and be simultaneously analyzed
