Midterm One
Introduction to Genetics
Genetics:
Definition: Study of heredity and the variation of inherited characteristics in populations.
Genes are DNA sequences that code for a product, located within the DNA that makes up chromosomes.
Phenotype: outward characteristics (something that can be measured or observed between cells or individuals.
Phenotype = genotype + environment
Genotype: what a phenotype is dependent on (genetic material of the organism).
Mono-genetic traits: These are traits that are determined by only one gene rather than numerous genes.
Gene expression: Controls the use of genetic information.
Chromosome segregation: Determines inheritance of alleles.
Random mutations: in genes lead to changes in the phenotype and Natural selection allows for evolution in populations.
Chromosomes: physical molecules that are passed on through generations (contain genes).
Karyotype:
Maternal and paternal (homologous chromosomes).
Genes: Sequence of DNA that encodes for a functional gene product -> Proteins
20,000-30,000 in humans.
Some code for mRNA and protein
Some code for RNA functional products (tRNA, rRNA, microRNA, etc).
Non-genetic regions on chromosomes
Have their own bit of sequence in which they can vary, which can sometimes affect the areas that include the genes, but may have other consequences
Codons: correspond to one amino acid depending on sequence of it
Used in process of translation (language of nucleic acids, then translates to amino acids within protein)
Genome: all of different DNA in cells that control phenotype and can be passed on
Units of information within genome
Chromosomes (physical DNA entities that can be passed through reproduction through generations)
Nuclear or mitochondrial genome
Portion of genome that codes for protein is ~2-4%
Genome = DNA molecules = DNA sequences
Why study genetics?
Variation = source of human disease
Greater variation within rather than between human populations
85% of variations within human exists within populations
Desire to help and treat others
Variation > gene > proteins > function > biology
Evolutionary connection: tied to natural selection/ evolution
Variation within species to understand how they evolved from common ancestors
Genetic studies:
Forward genetic screen: start with a desired phenotype and induce mutations (unbiased, mutagen)
Look for phenotype of interest induced by new mutations
Collect individuals with phenotype
find which genes mutated
Reverse genetics:
Start with gene of interest and make mutations specifically in that gene through various methods, then look for phenotype
Agarose Gel electrophoresis sorts DNA molecules by size
Gel electrophoresis:
Separates DNA molecules based on size.
Size is determined by the number of base pairs.
DNA sample is placed at one end of a porous gel and will run to the positively charged electrode since DNA is negatively charged.
Current is then applied and DNA molecules move from the negative electrode toward the positive electrode.
The longer the molecule the slower it will go, meaning when they take the snapshot of it, it will be closer to the wells.
The shorter molecules will move faster as there is less bulk on it and will be closer to the bottom of the page.
The well is where the sample is being placed at the atart.
Power is then turned on and DNA fragments migrate through the gel.
The negative is always at the top running down to the positive bottom.
A ladder is a known size of the DNA.
The size of the DNA = number of nucleotides = length
The size of RNA = number of nucleotides = length
The size of the Protein = number of amino acids, measured in kilo Daltons (unit of molecular weight).
Restriction Enzymes
They cut the double-stranded DNA at a specific sequence.
The cleavage occurs at the beginning of coding on either end and they become sticky as one piece of DNA becomes two.
Use:
For those undergoing sickle cell diagnosing, the genotyping uses restriction enzymes to distinguish between the alleles.
Wild Type: WT is the functional gene product.
The normal allele.
Punnett Squares: Basics
Punnett square: used to predict outcomes of a monohybrid cross
Start with genotype of parents (diploid)
Predict possible gamete genotypes (haploid)
Arrange possible gametes on edge of square
Fill in offspring squares using gametes from both parents
Gene Structure & Function, Genotype-Phenotype & Mutations
The human genome is also made up of the DNA found in the mitochondria.
Each cell in your body has ~200 - 2,500 mitochondria and each mitochondria has ~2-10 copies of the mtDNA.
Not homozygous or heterozygous for a singular gene since there are two plus copies for every single one.
2 - 10 copies of a gene in a mitochondria.
>200 mitochondria per cell.
All somatic cells contain the same genome.
Sometimes more or less copies and random mutations, but all contain the same DNA and gene sequences.
Germ line (germ cells): haploid, 23 chromosomes (n)
Somatic cells: diploid, 46 chromosomes (2n)
DNA is a code:
There are three informational entities on a chromosome:
Transcribed (expressed)
Not transcribed (has function)
Not transcribed (no function)
As we know more, we find out that there is no part of the sequence that doesn't have a function.
Transcribed and expressed:
5’ UTR (5' Untranslated Region): The region of mRNA before the start codon that is not translated into protein; it plays a role in regulation and ribosome binding.
3’ UTR (3' Untranslated Region): The region of mRNA after the stop codon that is also not translated; it can influence mRNA stability and translation efficiency.
Coding Sequence for tRNA: The segment of DNA or RNA that specifies the sequence of a transfer RNA (tRNA) molecule, which helps bring amino acids to the ribosome during protein synthesis.
Coding Sequence for rRNA: The segment of DNA or RNA that specifies the sequence of ribosomal RNA (rRNA), which is a structural and functional component of ribosomes.
Introns: Non-coding segments of a gene that are transcribed into pre-mRNA but are removed during RNA processing before translation.
Exons: Coding segments of a gene that are transcribed into pre-mRNA and retained in the final mRNA; they are translated into the protein.
Ribosome Binding Site (RBS): A sequence on the mRNA that is recognized by the ribosome, facilitating the initiation of translation.
Not Transcribed and Has a Function
Enhancer: A DNA sequence that increases the likelihood of transcription of a particular gene by providing binding sites for transcription factors.
Terminator: A sequence of DNA that signals the end of transcription, causing RNA polymerase to stop synthesizing RNA.
Origins of Replication: Specific locations on the DNA where replication begins, allowing the DNA to be copied.
Centromere: The region of a chromosome that links sister chromatids and is essential for proper chromosome segregation during cell division.
The cell has microtubules that grab onto the centromere of sister chromatids to move them as needed during mitosis and meiosis.
Found in everything / necessary if not there the chromosome cannot separate and gametes cannot form properly. This will cause NDJ when there is improper separation.
Promoter: A DNA sequence located at the beginning of a gene that provides a binding site for RNA polymerase and initiates transcription.
Start Codon: The specific sequence (usually AUG) in mRNA that signals the start of translation, marking where the ribosome begins to synthesize a protein.
Stop Codon: A sequence in mRNA (such as UAA, UAG, or UGA) that signals the end of translation, prompting the ribosome to release the newly formed protein.
Gene Structure:
Codons can be at the middle or end of the exon so that it does not get coded out.
Promoter: This is a regulatory region located upstream of the coding sequence. It is where RNA polymerase binds to initiate transcription.
They have specific sequences, such as where the RNA polymerase binds before beginning transcription.
Exons: These are the coding regions of the gene that contain the actual information needed to produce a protein. Exons are transcribed into mRNA and translated into amino acids.
Introns: These are non-coding regions interspersed between exons. They are transcribed into pre-mRNA but are spliced out during RNA processing before translation.
Enhancers: These are regulatory sequences that can be located far from the gene they regulate. They help increase the likelihood of transcription by binding transcription factors.
Silencers: These are also regulatory sequences that can inhibit transcription when bound by specific proteins.
Terminator: This signals the end of transcription. It tells RNA polymerase when to stop synthesizing RNA.
UTRs (Untranslated Regions): These are regions at the beginning (5' UTR) and end (3' UTR) of the mRNA that are not translated into protein but play roles in regulation, stability, and translation efficiency.
Mutations:
If you mutate an enhancer and it’s a non-neutral mutation what might occur?
There will be changes in the transcription binding (inc. or dec. the transcription amount) meaning that expression of the gene will inc. or dec. based on the changes. It also may change the circumstances of when it will be expressed leading to various issues.
If you mutate the coding sequence of a gene for a transcription factor with a non-neutral mutation, what might occur?
The coding sequence changes can cause an alteration of function as it affects whether or not the ribosome can bind to it in order to create a functional product/protein.
Termination Sites: These are specific sequences in the DNA that signal RNA polymerase to stop transcribing RNA. When RNA polymerase reaches these sequences, it detaches from the DNA.
Splicing: is performed by spliceosome- introns are cut out and the exons are brought together.
If the splicing occurs wrongly and parts of the intron are left inside will this make the sequence longer or shorter?
This will make the sequence longer on average, as the introns are a large length of code and it may include a stop codon so if there is a stop codon the code will be shorter in total (if).
It can also cause the exon to be spliced instead of after the intron.
The start codon is the first codon of an mRNA transcript translated by a ribosome.
The start codon always codes for methionine in eukaryotes and is coded as AUG.
The start codon determines the reading frame; this is a set of 3 nucleotides that are read as a small unit by the mRNA.
Translation occurs after the smaller unit binds to the larger ribosomal subunit.
The stop codon is a terminator codon within the mRNA that signals a termination of translation.
Stop codons signal the termination of translation by releasing the factors wich cause the ribosomal subunits to disassociate, releasing the amino acid chain.
UAA, UGA, and UAG
Translation occurs in protein coding until the stop codon is reached.
Ribosome Binding Site: specific sequences just upstream of the start codon.
This affects the amount of translations that will occur.
Name: DNA, RNA. or Protein Function: | ||
Central Dogma:The central dogma of biology is the process by which genetic information flows within a biological system. It can be summarized simply as:
DNA → RNA → Protein
DNA: Contains the genetic instructions.
Transcription
RNA: Transcribes the information from DNA to serve as a template.
Translation
Protein: Translates the information in RNA to perform various functions in the cell.
Trait: physical, behavioral, medical characteristics of an individual.
Transcription occurs in the nucleus and translation occurs in the cytoplasm.
Gene expression is regulated by proteins
Protein coding genes in prokaryotes and eukaryotes
Mutations that affect proteins:
Silent (synonymous):
DNA change that doesn’t alter protein
Missense (nonsynonymous):
DNA change that substitutes one amino acid for another
Nonsense:
DNA change that introduces a premature stop codon
Results in a shortened protein
Indel: insertions or deletions of nucleotides
Add or remove amino acids in a protein
If they are in multiples of 3
Frameshift: insertion or deletion of non 3 multiple nucleotides
Changes the reading frame of coding sequence
Defective or new function
Not likely to be functional or fold properly.
Frameshift mutations only happen in the translated region or if an exon is excluded and the loss of that shifts the reading frame.
This would be an insertion/deletion in the 5’ region
Duplication:
Either of nucleotides within a gene/multiple genos
Transposition
Swapping of DNA sequences within/ between chromosomes
Gene/ chromosome fusions
Duplication/expansion:
Expansion of repeat region
Chromosomes:
23 pairs in humans (46 total)
Chromosome makeup: karyotype
Can describe sex based on makeup of sex chromosomes
22 pairs of autosomes (1 pair of sex chromosomes (X, Y))
XX= female
XY= male
Biggest chromosome = 1
Smallest = 22
Visible chromosomes are made of highly condensed and organized chromatin
Features are important for replication and hereditary
Features:
Telomeres: ends of chromosomes
Lack genes
Consist of highly repetitive sequence
Heterochromatin (highly condensed)
Replication origins:
Thousands per chromosome on a EUK cell
Centromere:
1 per chromosome
Attachment site for microtubules during cell division
Karyotypes are taken from mitotic cells and consist of duplicated chromosomes
Consists of homologous chromosome pairs with duplicated sister chromatids
Sister chromatids: identical copies of a chromosome due to DNA replication
Homologous chromosomes: different versions of each chromosome (1 from each parent)
Contain the same genes
Allele: different version of a gene
AA= homozygous
Bb= heterozygous
Uppercase: dominant
Lowercase: recessive
Wild type: referent gene expression/ expression of parent allele
Haploid and diploid life stages:
Haploid: 1 version of each chromosome (humans: n= 23)
N= # of chromosomes
Diploid: 2 versions of each chromosome (humans n= 46)
Sperm or egg (each have haploid # of chromosomes)
If an organism is diploid it means that there are two copies of each chromosome and then you need to assume knowledge of dominance,
Homozygous Dominant: A/A
Homozygous Recessive: a/a
Heterozygous: A/a
Fertilization: go from 1n to 2n (copy from each of the gametes)
1st cell to form: zygote (diploid cell)
Zygote forms then divides many times to create a diploid multicellular organism
Subset of those cells can undergo meiosis
In meiosis, they start as diploid, then divide and produce haploid cells
Happens because of mitosis
Alleles (genotype), dominance, GOF/LOF, and phenotypic outcomes
Loss of Function and Gain of Function
Loss of Function
If one allele is a loss of function allele the other, functional will be dominant (recessive).
LOF means loss or reduction of the protein’s function
If one copy is enough to compensate for the loss of the other allele it will considered dominant
The other is recessive to wild type.
WT is haplosufficient.
Gain of Function
If one allele is gain of function allele, that allele will be dominant
New function or an increase of function.
GOF means an increase in protein function or the gaining of a new function overall.
If the GOF masks or overrides the effect of the other allele or it has a new function that the WT allele does not (so you see an additional phenotype) it will be dominant, though sometimes it may only be partially dominant.
What would be an LOF or GOF in RNA polymerase?
What is the function of RNA polymerase?
The transcription of the RNA molecule.
A LOF would then be:
A dec or no transcription
A GOF could be:
A inc of RNA/transcription
Can transcribe new types of genes.
rRNA that are pol 1 can now transcribe pol 11 for example.
Example of GOF:
Cells can gain stability to not be degraded or it can be a gain of ability to prevent degradation.
One mutant gene overrides WT and proliferates.
Phenotype: A phenotype is the composite of an organism’s observable characteristics or traits.
Includes:
Morphology
Development
Biochemical or physiological properties
Phenology (seasonal changes)
Behavior and products of behavior
An intermediate phenotype is one that shows aspects of both the WT and the mutate phenotype.
Also known as partially dominant.
Dominance depends on what phenotype is chosen to define dominance.
Haploinsufficiency: A single copy of the WT allele is insufficient to produce the normal or WT phenotype.
One wildtype allele is not enough to produce the WT phenotype.
Needs to be homogeneous in order to produce a phenotype.
It's not all or none, but it does need to meet a threshold.
Haplosufficiency: A single copy of the WT allele is sufficient to produce the normal or WT phenotype.
One wild type allele provides all of the necessary protein/phenotype.
Can be heterozygous.
Pedigree: genetic inheritance through families
Square= male — XY
Circle= female — XX
Filled in shape= affected individual
Line connecting shapes= mating
Two lines indicate that the parents are related.
Pseudodominance: recessive phenotype showing up even if there are not 2 alleles for that particular gene
Hemizygous: alleles for which there is only one copy
Difficulties of inheritance of human traits:
Long generation time
Data must be obtained from offspring produced
Experimental mating not possible
Limited sample size
What is a pedigree:
Orderly array of family info
Important in predicting genetic risk
Often incomplete
Can also rely on phenotypes/ disease
Coinheritance of molecular markers: (ways of tracking specific DNA sequence that may cause a particular trait or be close to on the chromosome)
Sequence tagged sites
All sections of the chromosomes with known DNA sequence that varies
Types of problems:
Determining:
Inheritance type
Autosomal, recessive
Autosomal, dominant
X linked, recessive
X linked, dominant
Y linked dominant/ recessive
Genotypes for various individuals
Probability of an affected offspring
Autosomal Dominant:
One of the parents must have that trait.
There is male to male transmission.
Traits don’t skip a generation.
There are multiple modes of inheritance.
Autosomal Recessive:
Parents might not express the trait, they can but not necessarily.
Rare traits are caused by recessive mutant alleles that are more prevalent in offspring of consanguineous partners.
X-linked Dominant:
Females can pass on the trait to both daughters and sons.
Males will pass on to all females but no males.
X-linked Recessive:
Trait is more common in males.
Affected mothers will pass it to all sons.
Affected males can only pass it to daughters if mated to an affected or carrier female.
Since male parents only donate Y chromosomes to male offspring, they cannot pass it to sons.
Maternal inheritance:
Females pass on the trait to all of their children because the mitochondria comes from females in the zygote, but males cannot pass on the trait.
Does not follow dominant/recessive patterns.
There’s more than 2 alleles of mitochondrial genes in every cell in your body. If too many alleles are mutant then the trait will shop up.
Mutation prevents mitochondria from making proteins from mitochondrial genes.
Maternally inherited as sperm does not have mitochondria.
Codes from some polypeptides of the mitochondrial respiratory chain.
100,000 mitochondria per fully-grown human oocyte.
2-10 copies of mt chromosomes per mitochondria.
Children will have the same genotype as mom, variation in copy number of WT vs Mutant mtDNA.
Y-linked pattern inheritance:
Recessive traits typically skip generations
Recessive autosomal traits appear equally in both sexes
Either 1-3 or 1-4 must be heterozygous
Affected individuals all have affected parent
Dominant autosomal traits appear equally in both sexes
Dominant traits almost always appear in each generation
Strategies:
Hypothesize a type of inheritance and see if consistent
Is the trait rare? Unless stated otherwise, assume it’s rare
Establish if trait is dominant or recessive
If most males affected, likely to be X linked recessive
If males pass on to sons cannot be X linked
Outsiders:
For dominant pedigrees:
Assume affected outsiders are heterozygotes
For recessive pedigrees:
Assume normal outsiders are homozygotes
Genotype and Factors that influence phenotype:
Two organisms can have the same genotype but the temperature or other environmental factors can affect the gene activation.
Incomplete Penetrance
Penetrance: The percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype.
Incomplete penetrance: Not everyone with the genotype will have the same phenotype.
Like ⅓ of the family with the mutation has the disease = 33% penetrance.
Variable Expressivity:
All of the individuals that have the same disease / phenotype have different onset, severity, distribution, and presence of the associated feature.
What symptoms they have for the phenotype is variable despite the same genotype.
Some will have the normal expression of the mutation.
Others will have novel mutations.
Novel mutations: the first type these mutations have appeared in conjunction with the genotype.
Comparing Expressivity and Penetrance:
Each “individual” shown has the same genotype.
Penetrance is about whether or not a trait is expressed (yes or no), while expressivity is about the variability in the expression of that trait among those who do express it (how much or how severe).
Null = no protein function
Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease.”
Mutation type:
Missense vs silent mutation
Copy number variants
Number of copies of the gene
Modifier genes
Genes for transcription factors
Complex gene networks that code for multiple genotypes and phenotypes that modify expression of that trait.
Digenic mutations
Mutations in 2 genes
Oliogenic mutations
Mutations in a few genes
Allele Dosage
Number of given alleles 1, 2, 3, or more?
Number of copies of the ___ gene that changes in response to drugs.
Environment
This is not just an organism’s surroundings, but anything that can alter or influence a phenotype, including personal decisions.
Actionable choices that you make.
Epigenetic modifications
Modifications to DNA that do not change DNA sequence.
Gene expression level
How many transcripts are being made.
There are three factors that influence phenotype:
Genetics, Epigenetics, and Environments
Changes that alter the physical structure of DNA without altering the DNA sequence. These changes can influence if the promoter or enhancer region of a gene is accessible or not for instance.
Monozygotic Twin Studies:
Same genome
Raised in different environments
Compare phenotypic differences
Qualitative experiments: cannot determine the percentage because it will never be 100% on what causes certain things.
Two issues: one is that with humans it is ethical to separate them and two it is hard to control the environment. Ultimately the sample size is always going to be low.
Mono vs Di twins
Dizygotic twins
Two embryos that were implanted
Different DNA: ~50% shared
Same environment
If intelligence is different in: genetics
If intelligence is same in: environment
Monozygotic twins
A single zygote that splits into two, one egg and one sperm
Same DNA
Different Environment
If intelligence is different in: environment
If intelligence is same in: genetics
Concordance:
The measurement of shared traits.
The degree to which siblings share a particular trait or genetic characteristic. It is often used in the context of twin studies or sibling studies to assess how often both siblings exhibit the same phenotype (observable traits) or genotype (genetic makeup) for a specific condition
For example, if both siblings have a genetic disorder, they are considered concordant for that disorder. If only one sibling has it, they are considered discordant. Concordance rates can provide insights into the genetic and environmental contributions to traits and diseases, helping researchers understand the heritability of specific conditions.
Greater than two means that there is a greater genetic component to these diseases.
Find the ratio by dividing one by the other.
The ratio is between mono and di twins.
Take Home Messages:
Genotype can influence phenotype at various levels.
RNA
Protein
Cellular Function
Whole organism
Genotype does not always predict phenotype
Genotype of other genes
Environmental factors
Epigenetic alterations
Need data to assess roles of genotype and environment:
DNA sequence comparison of affected vs unaffected individuals
Who has mutation and who does not?
Monozygotic twins, dizygotic twins, and sibling studies
Inbred model organism studies (plants, mice, drosophila, etc.)
AKA true breeding
Mitosis and Meiosis
Mitosis: purpose is to grow and repair itself
Done by somatic cells
Keep number of chromosomes the same
Meiosis: purpose is sexual reproduction and reduce # of chromosomes in the cell
Done by germ cells (meiocyte)
Only these contribute genetic information that will be passed on to next generation
Making a human…
Day One: Fertilization
This is the zygote.
It is single celled.
It undergoes mitosis to create more cells and go from an embryo to a developed human.
Day Two: Cleavage
Day Three: Compaction
Day Four: Differentiation
Day Five: Cavitation
Became you, your placenta, umbilical cord, etc.
Miotic divisions are how we go from embryo to developed human.
Why is it important that all cells are genetically identical?
It is important because it all comes from one cell that then continually divides.
Different genes turn on and off some of the expression, losing genetic information can be harmful:
A person gets an injury. During which some genes were turned off before that became activated in order to heal the wound.
Mitosis:
Can happen in both diploid and haploid cells
Parent cell has 3 chromosomes (diploid cell/ diploid # 6)
Parent cell = somatic
Occurs in somatic cells and produces two identical cells that are identical to the parent cell
Somatic means that anything that is not a gamete (germline cells)
2 daughter cells that result, also have 6 chromosomes
Genetically identical to parent
Start with parent cell in interphase before it divides
DNA replicated in interphase (S phase)
Prophase: identify chromatin and it is started to condense to visible chromosomes that can be seen within photos of the cell
Centrioles are duplicated and microtubules start to extend from those centrioles
Can see duplicated copies of each chromosome held together at centromere
Diploid # is 4
Prometaphase: centrioles move to opposite sides and the microtubules are extending out from centrioles, contacting centromeres in each homologous chromosome
Microtubules can then push on chromosomes until they align near center
Nuclear envelopes break down so tubules can come in contact with chromosomes
At each sister chromatin, there are groups of proteins connected at centromere, and they make up the kinetochore proteins (as well as cohesion), that serve as the attachment site for spindle microtubules that are connecting with centriole
Shugoshin proteins: stabilize connection between sister chromatids at the centromere region
Anaphase: connection between sister chromatids is broken and centromeres separate from another, leads to chromatids going to opposite polls of the cell, becoming separate chromosomes
Telophase: nuclear envelope reforms, form 2 separate nuclei (end of mitosis technically)
Division of nucleus: karyokinesis (separation of chromosomes)
Cytokinesis: cytoplasm and other cell components are divided
Track ploidy and chromosome copy during mitosis
Step one: Replicate each chromosome, while keeping the copies stuck together.
Interphase: DNA is replicated. Each chromosome is replicated to make two chromatids.
Step two: Line up the individual chromosomes along the middle of the cell, metaphase.
Step three: Separate the copies and put a full set into each daughter cell.
What distinguishes two different chromosomes from one another?
Size (# of base pairs)
Banding pattern (not a gene)
Condensed or open the allele is
Contromere location
Not always in the middle
Gene presence
Different DNA sequences
Different genes
Homologous chromosomes
Ploidy: the number of sets of chromosomes in a cell
Identify the Chromosome Number: Count the total number of chromosomes in a cell during metaphase of cell division (where chromosomes are most visible).
Determine the Base Number (n): Identify the haploid number (n), which is the number of chromosomes in a gamete (sperm or egg). For humans, n is 23.
Calculate Ploidy:
Haploid (n): One set of chromosomes (e.g., gametes).
Diploid (2n): Two sets of chromosomes (e.g., most human cells with 46 chromosomes).
Triploid (3n): Three sets of chromosomes (e.g., some plants).
Tetraploid (4n): Four sets of chromosomes (e.g., some species of frogs).
Practical Example: If you find 46 chromosomes in a human cell, it’s diploid (2n = 46). If a plant has 30 chromosomes, it’s haploid (n = 30), making the diploid number 60 (2n = 60).
(x)n =-__ x = number of chromosomes sets
__n = (y) y = the total number of chromosomes
Overview:
Chromosomes (homologous pairs if diploid) -> replicate (chromatids) -> chromatids separate = two identical cells (assuming no mutations).
Ploidy
2n = 6
2 types
6 chromosomes total
Mitotic Mutations:
Mitotic mutations are genetic changes that occur during the process of mitosis, which is the cell division that results in two identical daughter cells. As a result, one or more of the daughter cells may have a different genetic makeup compared to the original cell, potentially leading to conditions such as cancer if the mutations affect genes that regulate cell growth and division.
Mosaicism:
Mosaicism refers to the presence of two or more genetically different cell populations within the same individual, resulting from mitotic mutations or other genetic changes that occur after fertilization. This can happen when a mutation occurs in a single cell early in development, leading to some cells carrying the mutation while others do not. The result is a mosaic organism, where different tissues or areas may have distinct genetic compositions. Mosaicism can manifest in various ways, including variations in appearance, health conditions, or susceptibility to certain diseases.
Disjunction: The separation of sister chromatids during anaphase.
Non-disjunction: when these cells don’t separate.
Somatic mosaicism occurs through mutations during DNA replication or NDJ during mitosis.
Every cell in your body is not truly genetically identical.
Monozygotic twins are not genetically identical in every cell in their body.
Mitotic NDJ is one mechanism by which monozygotic twins can exhibit different phenotypes! Mutations during DNA replication are another.
Somatic mosaicism is when different genotypes become present.
A genomic view of mosaicism and human disease
Mosaicism refers to the presence of genetically distinct cells within an organism that result from postzygotic mutational events.
There are several different types of mosaicism at the organismal level that are categorized by the tissue distribution of the variant cells, including germline [cells that make gametes] mosaicism and somatic mosaicism.
Many different molecular types of genetic lesions — from single-nucleotide changes to large-scale chromosomal alterations — can be present in a mosaic form.
Mosaicism can be generated not only by mutations resulting in variant genotypes but also by the reversion or rescue of abnormal genotypes.
Mosaicism can lead to a diverse range of phenotypes, from overt to occult. It can also allow the clinical expression of mutations that would otherwise be lethal in the non-mosaic state, thus providing a broader assessment of genotype— phenotype correlations than germline-inherited disorders.
Modern genomic technologies have allowed the considerable frequency of mosaicism in humans to be increasingly recognized. For example, the frequency of chromosome aberrations in the early embryo has now been estimated ~70%.
Somatic Mosaicism: Turner's syndrome:
Female characteristics
Reduced ovaries
Differences in structure of neck and chest
Reduced breasts
No Barr bodies
2n=45 (-X)
Also called XO; missing one X chromosome
Some people with XX/XO:
There are two types of the cells in the body.
What could the starting genotype be?
The starting genotype is XX.
Meiosis:
Only happen with diploid cells
Involves independent assortment of homologous chromosomes
2 rounds of cell division
Parent cells are germ cells
Daughter cells have half # of chromosomes compared to parent cells
Genetically different from parent cell and each other
When chromosomes line up in pairs: called a tetrad
Homologous chromosomes synapse
Line up and are joined together to form tetrads
Prophase 1: consists of synapsis and crossing over, and the formation of tetrads
Chromosomes have all been copied (DNA replication already occurred)
Leptotene: beginning of chromosome condensation (still long and hard to identify individual chromosomes)
Start to form bivalents that still each have 2 sister chromatids attached
Zygotene phase: chromosomes still long, can identify the chromosomes as they are starting to pair/ synapse homologous chromosomes
Pachytene phase: can see both homologous chromosomes and can see sister chromatids for each chromatid
Chromosomes are thickening
Fully synapsed
Crossing over is occurring
Each of the 2 sister chromatids of the homologous chromosomes all line up together during synapse, and they stick together by proteins cause cohesins that form rings to keep 2 sister chromatids attached
Have a break in the DNA of each homologous chromosome (non-sister chromatids)
Then you have joining of 2 non sister chromatids
If no crossing over, chromosome will be contiguous
Results in creation of recombinant chromosomes
The goal of Meiosis is to make haploid gametes.
Meiosis Steps:
Meiosis I
Prophase I:
Chromosomes condense and become visible.
Homologous chromosomes pair up (synapsis) and exchange genetic material through crossing over.
The nuclear membrane begins to break down.
Metaphase I:
Paired homologous chromosomes line up along the equatorial plane of the cell.
Spindle fibers attach to the centromeres of each homolog.
Anaphase I:
Homologous chromosomes are pulled apart to opposite poles of the cell.
Each pole receives one chromosome from each pair.
Telophase I:
Chromosomes reach the poles and begin to de-condense.
The nuclear membrane may reform, resulting in two nuclei.
Cytokinesis I:
The cell divides into two daughter cells, each with half the original number of chromosomes (haploid).
Meiosis II
Prophase II:
Chromosomes condense again, and a new spindle apparatus forms in each daughter cell.
The nuclear membrane breaks down if it reformed.
Metaphase II:
Chromosomes line up along the equatorial plane in each daughter cell.
Anaphase II:
Sister chromatids are pulled apart to opposite poles of the cell.
Telophase II:
Chromatids reach the poles and begin to de-condense.
The nuclear membranes reform around each set of chromosomes.
Cytokinesis II:
Each of the two daughter cells divides again, resulting in four haploid gametes.
Similarities
Both somatic and germ cells have to do chromosome duplication before division
Happen as part of the normal life cycle of the cell
Divisions of phases of cell cycle:
Either dividing or not dividing (interphase)
Interphase: 4 parts
First: G1
Cell is waiting for signal to divide
No signal, then will enter G0 (phase for non dividing cells, exiting from cell cycle)
Yes signal, reenter cell cycle, back to G1, and prepare to copy DNA by making all proteins necessary to synthesize and duplicate DNA
Phase for growth and signal waiting
Second: S phase (synthesis)
DNA replication happens
If you started with 1 chromatid, by end of S phase, you have 2 identical copies held together at centromere
Decided that it will divide if it goes to S phase
After completes replication, enters G2
During G2, it prepares proteins necessary for cell division
Enters mitosis
Checkpoint proteins regulate progression
Cyclin protein: goes through cycle of degradation and stability during different stages of cell cycle
Cyclin dependent kinase protein: phosphorylate key components that help it progress through cell cycle
Checkpoint between G1/ S: monitors cell size and integrity (damage to chromosomes)
Checkpoint between G2/ mitosis: monitors completion of DNA synthesis and checks for DNA damage
Mitosis checkpoint: monitors spindle formation and attachment to kinetochores
Each tetrad separates in anaphase 1 and the homologs (pair of homologous chromosomes) independently separate into the 2 daughter cells of meiosis 1
Humans have 2^(33)= 8,388,608 possible chromosome combinations per gamete (1 sperm/egg)
But you have to have 2 gametes come together
1/70,368,744,177,664 to get YOU
This is how meiosis shuffles genetic information
This shows how many possibilities for allele combination with independent assortment AND crossing over
Fertilization:
Sperm smaller than egg
Germ cell that rises to sperm: spermatogonium
Germ cell that rises to egg: oogonium (oocyte)
Spermatocytes: (males)
Form during puberty
Constantly undergoing meiosis
Produces 4 equivalent spermatozoa
Equal cytoplasmic division
Oocyte: (female)
Form in the embryo
Start entering meiosis in embryo
Pause in the middle of prophase 1
Reanimated in puberty
Doesn’t complete until fertilization
Creates 1 ovum per oocyte + 2 polar bodies
Unequal cytoplasm division
Sexually reproducing organisms’ cycle through haploid and diploid life stages
Ex: bdelloid rotifer and aspidoscelis neomexicana only have females in their species
They go through parthenogenesis
Start with an oocyte and it undergoes meiosis and forms secondary oocyte and 1st polar body
Then it makes the ovum and left with 3 polar bodies
1st polar body undergoes cell division= 4 total haploid cells produced
Inside female body, one of the daughter cells of primary oocyte will go back and fuse with ovum that is created, that makes a diploid cell that can be activated and form a zygote
Disjunction: separated the sister chromatids
Nondisjunction: failure of separation
Nondisjunction in meiosis creates gametic aneuploidy
Homologous chromosomes failure to separate
Results in 1 cell having 2 homologous chromosomes and 1 cell that has none
Result in all gametes having different # of chromosomes