Chapter 11: Human Genetic Variation (and Chapter 15.2 Chromosomal Abnormalities)
What is the difference between variant and mutation?
same thing
SNP Point mutations????????
substitution
deletion/ addition
Copy number variation (CNV)
polyploidy
Aneuploidy
Mixoploidy
Recombination errors
chromosome cross-over during mitosi
Chromosomal
Translocations
Duplications
Inversions
Indels/Delins
DNA replication errors:
replication slippage → deletion or expansion ( especially during very repetitive strands
causes Huntington disease ( accumulation of toxic debris) → CAG repeats → Q( glutamine accumulation)
Base damage
reactive oxygen species(ROS) proudes during normal metabolic processes can damage DNA base
Strand breaks
single strand breaks
double-strand breaks
Chromosomal abnormalities
Chemical damage
hydrolytic most common damage to DNA → depurination the most common hydrolic damage of DNA
reactive oxygen species(ROS)
Methylation
Polyploidy → an extra set of chromosomes ( lethal/ not viable)
aneuploidy → abnormal number of chromosomes ( a single chromosome is multiple or missing)
example of aneuploidy where the people survive
trisomy 21
super male (XYY)
chromosome 18
mixoploidy → some cell have mutations that result in different number of chromosome sets → cause mosaicism (lethal)
Robertsonion Translocation (centric fusion)
translocation in chromosomes but two parts of the chromosome that attach have two nearby centromeres. Both centromeres fuse together and don’t cause a problem during further mitosis → genetic information is not lost
occurs during DNA synthesis when the leading strand is misaligned with the leading strand template
Polymerase can slip back wars or forward, causing an insertion or deletion
all of this can cause egntic disorders and diseases
Fragile X syndrome is a genetic disorder caused by an expansion of the CGG repeat in the FMR1 gene on the X chromosome. This results in reduced or absent production of the FMR1 protein, leading to a range of cognitive and behavioral problems. It is an X-linked dominant disorder, affecting males more severely than females because female shave another X and, therefore FMRI1 gene.
Radiation
UV
Xrays
chemicals
cigarette smoke
nitrate and nitrate preservatives
benzoyl peroxide
Infectious agents
HPV
Heliobacter pylor
Cp(phosphate)G island
CGCGCGC
found in promoters but not actively transcribed
when the C get methylated( which it easily done C→T) then there is no transcription
if bases are mismatched, then they don’t fit together and the following bases are also wonky
The polymerase also notices and pauses replication and uses exonuclease activity to remove the incorrect nucleotide.
only used in emergencies because there is no proof reading
cancer
apoptosis
balanced variation → all of the gentic martial is still there
NO net loss or gain
Translocations
Inversions
Point mutations
unbalanced → not all genetic material
Change in copy number
Abnormal chromosome segregation
Point mutations
Example: Philadephia chromosome
when chromosome 9 and chromosome 22 break and exchange portions
causes Leukemia
Satellite DNA: highly repetitive noncoding region if the genome, located near the centromeres and telomeres region of chromosome
why is replication slippage more common?
when the DNA polymerase enzymes slips from the DNA strand and adds or deletes on e or more repeats
if slippage occurs pieces still fit together and polymerase is unable to detect if they made a mistake
Type of Variation | Definition | Similarities | Differences |
---|---|---|---|
SNV | A single nucleotide change in the DNA sequence | Can occur anywhere in the genome; can be a germline or somatic mutation | Only involves a change in a single nucleotide base |
SNP | A type of SNV that is present in at least 1% of the population | Can occur anywhere in the genome; can be a germline or somatic mutation | Must have a minor allele frequency of at least 1%; used as genetic markers in association studies |
Indel | A small insertion or deletion of DNA sequence | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the addition or removal of one or more nucleotides |
CNV | A large segment of DNA that is duplicated or deleted in the genome | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the gain or loss of a large segment of DNA; can be variable in size |
VNTR | A region of DNA where a short sequence of nucleotides is repeated in tandem | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the gain or loss of a variable number of tandem repeats; can be used as genetic markers in forensics and population genetics |
Note: Germline mutations occur in the DNA of sperm or egg cells and are passed on to offspring, while somatic mutations occur in non-reproductive cells and are not passed on to offspring.
1000Genome project: indicated in 2008 in 26 different population
goal: search for de novo mutations
found that African populations had the most variations in genome and Europe, east Asia and South Asia least variation
→ founders effect
Telomere to telomere consortium: focused on identifying the first complete assembly of human genome with euchromatic and heterochromatic region8 coding and non-coding)
Functional constraint: parts of DNA genome is silenced through methylation and phosphorylation
Most protein variation have a neutral effect and not necceraly cause a a dise( example blood groups)
functional constrains 1.2% of DNA can´t change the protein because they are so important
but more because of regulation
promoter regions and enhancers
blood group
Cytogenetics: branch of genetics and biology concerned with chromosomal behavior
FISH: a molecular cytogenetic technique that allows the localization of a specific DNA sequence or an entire chromosome in a cell
for Philadelphia Chromosome: tag both chromosome with different fluorescence molecules and take multiple pictures of translocation
G-banding: A type of standing with Giemsa stain
DNA from white blood cells during prometaphase ( as condenst)
dark color= AT-rich → gene poor→ hetero chromatin
light color= GC rich → gene-rich
position of centromere
Metacentric (center)
Submetacentric (between middle and telomere)
Acrocentric (near telomere)
penetrance
anticpation
repication slippage
dynamic
18
5 open
1 hardy weinberg
bonus
What is the difference between variant and mutation?
same thing
SNP Point mutations????????
substitution
deletion/ addition
Copy number variation (CNV)
polyploidy
Aneuploidy
Mixoploidy
Recombination errors
chromosome cross-over during mitosi
Chromosomal
Translocations
Duplications
Inversions
Indels/Delins
DNA replication errors:
replication slippage → deletion or expansion ( especially during very repetitive strands
causes Huntington disease ( accumulation of toxic debris) → CAG repeats → Q( glutamine accumulation)
Base damage
reactive oxygen species(ROS) proudes during normal metabolic processes can damage DNA base
Strand breaks
single strand breaks
double-strand breaks
Chromosomal abnormalities
Chemical damage
hydrolytic most common damage to DNA → depurination the most common hydrolic damage of DNA
reactive oxygen species(ROS)
Methylation
Polyploidy → an extra set of chromosomes ( lethal/ not viable)
aneuploidy → abnormal number of chromosomes ( a single chromosome is multiple or missing)
example of aneuploidy where the people survive
trisomy 21
super male (XYY)
chromosome 18
mixoploidy → some cell have mutations that result in different number of chromosome sets → cause mosaicism (lethal)
Robertsonion Translocation (centric fusion)
translocation in chromosomes but two parts of the chromosome that attach have two nearby centromeres. Both centromeres fuse together and don’t cause a problem during further mitosis → genetic information is not lost
occurs during DNA synthesis when the leading strand is misaligned with the leading strand template
Polymerase can slip back wars or forward, causing an insertion or deletion
all of this can cause egntic disorders and diseases
Fragile X syndrome is a genetic disorder caused by an expansion of the CGG repeat in the FMR1 gene on the X chromosome. This results in reduced or absent production of the FMR1 protein, leading to a range of cognitive and behavioral problems. It is an X-linked dominant disorder, affecting males more severely than females because female shave another X and, therefore FMRI1 gene.
Radiation
UV
Xrays
chemicals
cigarette smoke
nitrate and nitrate preservatives
benzoyl peroxide
Infectious agents
HPV
Heliobacter pylor
Cp(phosphate)G island
CGCGCGC
found in promoters but not actively transcribed
when the C get methylated( which it easily done C→T) then there is no transcription
if bases are mismatched, then they don’t fit together and the following bases are also wonky
The polymerase also notices and pauses replication and uses exonuclease activity to remove the incorrect nucleotide.
only used in emergencies because there is no proof reading
cancer
apoptosis
balanced variation → all of the gentic martial is still there
NO net loss or gain
Translocations
Inversions
Point mutations
unbalanced → not all genetic material
Change in copy number
Abnormal chromosome segregation
Point mutations
Example: Philadephia chromosome
when chromosome 9 and chromosome 22 break and exchange portions
causes Leukemia
Satellite DNA: highly repetitive noncoding region if the genome, located near the centromeres and telomeres region of chromosome
why is replication slippage more common?
when the DNA polymerase enzymes slips from the DNA strand and adds or deletes on e or more repeats
if slippage occurs pieces still fit together and polymerase is unable to detect if they made a mistake
Type of Variation | Definition | Similarities | Differences |
---|---|---|---|
SNV | A single nucleotide change in the DNA sequence | Can occur anywhere in the genome; can be a germline or somatic mutation | Only involves a change in a single nucleotide base |
SNP | A type of SNV that is present in at least 1% of the population | Can occur anywhere in the genome; can be a germline or somatic mutation | Must have a minor allele frequency of at least 1%; used as genetic markers in association studies |
Indel | A small insertion or deletion of DNA sequence | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the addition or removal of one or more nucleotides |
CNV | A large segment of DNA that is duplicated or deleted in the genome | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the gain or loss of a large segment of DNA; can be variable in size |
VNTR | A region of DNA where a short sequence of nucleotides is repeated in tandem | Can occur anywhere in the genome; can be a germline or somatic mutation | Involves the gain or loss of a variable number of tandem repeats; can be used as genetic markers in forensics and population genetics |
Note: Germline mutations occur in the DNA of sperm or egg cells and are passed on to offspring, while somatic mutations occur in non-reproductive cells and are not passed on to offspring.
1000Genome project: indicated in 2008 in 26 different population
goal: search for de novo mutations
found that African populations had the most variations in genome and Europe, east Asia and South Asia least variation
→ founders effect
Telomere to telomere consortium: focused on identifying the first complete assembly of human genome with euchromatic and heterochromatic region8 coding and non-coding)
Functional constraint: parts of DNA genome is silenced through methylation and phosphorylation
Most protein variation have a neutral effect and not necceraly cause a a dise( example blood groups)
functional constrains 1.2% of DNA can´t change the protein because they are so important
but more because of regulation
promoter regions and enhancers
blood group
Cytogenetics: branch of genetics and biology concerned with chromosomal behavior
FISH: a molecular cytogenetic technique that allows the localization of a specific DNA sequence or an entire chromosome in a cell
for Philadelphia Chromosome: tag both chromosome with different fluorescence molecules and take multiple pictures of translocation
G-banding: A type of standing with Giemsa stain
DNA from white blood cells during prometaphase ( as condenst)
dark color= AT-rich → gene poor→ hetero chromatin
light color= GC rich → gene-rich
position of centromere
Metacentric (center)
Submetacentric (between middle and telomere)
Acrocentric (near telomere)
penetrance
anticpation
repication slippage
dynamic
18
5 open
1 hardy weinberg
bonus