Exam 1 Flashcards
Major Events in Genetics
9-10,000 BC: Domestication of Plants and Animals’
1859: Charles Darwin published Origin of the Species
1866: Mendel published paper on Genetics of Pea Plants
1871: Miescher: Isolated DNA
1883: Galton: Eugenics
1909: Garrod: Inborn errors of Metabolism
1941: Beadle and Tatum: One gene=one enzyme
1944: Avery, Macleod, & McCarty: DNA is genetic material
1953: Watson and Crick: Structure of DNA
1956: Tijo & Levan: 46 chromosomes
1960: Elucidation of Genetic Code
2003: “Completion” of the Human Genome Project
Portrait of a chromosome
P arm: short arm
Q arm: long arm
Telomeres: The ends
Heterochromatin: Where the Chromosome is dark
Euchromatin: Where the Chromosome is light
Centromere: Constriction where the two chromosomes are attached
Genomics
Field that analyzes and compares genomes of different species
Genes
Parts of DNA that contain the instructions within the cells for RNA production
Gene Terminology (Promoter, Coding Region, Non-coding Region, UTR, Polyadenylation Signal
Promoter: sequence that signals start of a gene
Coding region: series of codons that represent the amino acid sequence
Non-coding region: outside of the region coding for the amino acid sequence
Untranslated Region: 3’ and 5’ - noncoding sequence at the ends of a gene
Polyadenylation signal - codes for addition of the poly-A-tail (a string of adenine based nucleotides to an RNA molecule to make it more stable and prevent degradation)
Nucleotide
Made up of a sugar, phosphate, and a nitrogenous base
The nitrogenous bases are adenine, guanine, cytosine, thymine, and uracil
Purine vs. Pyrimidine
Purine: the nitrogenous bases that have a two ring structure, adenine and guanine
Pyrimidine: the nitrogenous bases that have a one ring structure, thymine cytosine and uracil
Properties that Stabilize DNA (Bonds, Hydro-, & Charges)
Hydrogen Bonds - weak bond between the bases, billions between strands of DNA
Hydrophobic Bonds - Weak bonds between stacked bases
Phosphodiester Bonds - Strong covalent bonds between sugars
DNA is hydrophobic on the inside and hydrophilic on the outside
DNA is negatively charged on outside which allows for association w/ the positively charged histones
Human DNA
3 billion bp
25,000 genes
1.5% encodes for protein
5% codes for regulatory elements
50% unique sequence
DNA is in every cell except for RBCs
Chromosome 21 is the smallest w/ 50 million bp and 250 genes
Chromosome 1 is the largest w/ 250 million bp and 2,000 genes
Noonan Syndrome
Symptoms/Example:
Woman with short stature, pulmonary stenosis (narrowing of pulmonary valve), developmental delay, facial dysmorphology, webbed neck, sparse and very coarse hair, and sparse eyebrows and eyelashes
Cause: A cytosine was incorporated in place of a thymine, causing a single nucleotide substitution in the PTPN11 gene
Alleles
Variation of a gene that is not necessarily a mutation
Ex. Allele T - ACGTC Allele t - AGGTC
Every somatic cells contain two alleles (one from each chromosome)
If an allele leads to a disease it is called a mutant allele
Expressivity
The genotype is the alleles itself, but the phenotype is how the people actually turn out. Expressivity is how the change appears.
Complete/Fully Penetrant: When you have the genotype, you have the disease
Incomplete/Reduced Penetrance: When you have the genotype, you may or may not have the disease
Modes of Inheritance
For this test we only need to know the autosomal inheritance
This can be autosomal dominant or recessive
Huntington Disease is autosomal dominant because it affects both sexes and typically appears every generation
Cystic Fibrosis is autosomal recessive because it affects both sexes but can skip generations through carriers
Autosomal Dominant
Criteria:
1. Males and females can be affected, as well as male-to-male transmission can occur
2. Males and females transmit the trait with equal frequency
3. Successive generations are affected
4. Transmission Stops after a generation in which no one is affected
Phenotype (Genotype): Sick (DD or Dd) or Well (dd)
Autosomal Recessive
Criteria:
1. Males and females can be affected
2. Affected males and females can transmit the gene, unless it causes death before reproductive age
3. The trait can skip generations
4. Parents of an affected individual must be heterozygous or have the trait.
5. More likely to occur in families with consanguinity (incest)
Phenotype (Genotype): Sick (rr) or Well (Rr and RR)
Inheritance of Common Traits
Dominant: Dimples, Widow’s Peak, Freckles, and Cleft (Butt Chin)
Recessive: Round Cheeks, Straight hairline, no freckles, round chin
Inborn Errors of Metabolism and Phenylketonuria
Inborn Errors of Metabolism: disorder due to absent or altered enzymes, this causes too much substrate, too little product, or too much product, and affects the major biomolecules
Phenylketonuria (PKU): this is an example of an inborn error of metabolism
Cause: deficiency or abnormal Phenylalanine Hydroxylase enzyme (PAH). PAH converts the amino acid phenylalanine to tyrosine. W/o PAH the phenylalanine builds up in tissues and the brain, and patients become deficient in tyrosine. This build up of phenylalanine leads to mental retardation and behavior problems. The lack of tyrosine results in eczema, fair skin, and blue eyes because melanin cannot be produced from phenylalanine.
Compartmentalization
Definition: Areas of the cell that are isolated by at least one selectively permeable membrane
Compartments: cytosine, ER, Golgi apparatus, nucleus, peroxisome, lysosome, and mitochondria
Organelles vs. Structures
Organelles: nucleus, ER, Golgi apparatus, mitochondria, lysosomes, peroxisomes, and vesicles
Structures: cytoskeleton, cilia, flagella, microvilli, ribosomes, centrioles, centrosomes, and proteasomes
Lysosomes
Membrane-bound save containing more than 40 types of digestive enzymes which require an acidic environment. They remove or recycle bacterial remnant, worn-out organelles, and other materials like excess cholesterol. The enzymes also break down some digested nutrients into forms that the cell can use.
Tay-Sachs
Summary: This is a lysosomal storage disorder, and it is also an inborn error of metabolism
Cause: There is a deficiency of enzyme Hexosaminidase A, which causes GM2 ganglioside to accumulate in the lysosome.
Signs/Symptoms: progressive weakness, loss of motor skills, decreased attentiveness, increased startle response, progressive neurodegeneration (seizures, blindness, spasticity, death, all usually before 4 years old)
Plasma Membrane
Forms a selective barrier, it is a phospholipid bilayer because it has a phosphate end (hydrophilic) and a fatty acid chain (hydrophobic). It contains proteins (for active or facilitated diffusion), glycoproteins (for identifying the cell), and glycolipids (facilitate cell-to-cell interaction)
The proteins can have faulty protein channels which affects the ions (sodium, potassium, and chloride)
Cystic Fibrosis
Cause: due to mutations in the Cystic Fibrosis Transmembrane Receptor (CFTR). CFTR is a chloride ion channel. There are several different mutation types, but in general, the mutations prevent movement of chloride ions out of cells. This causes the ions to be trapped in the water inside of cells. Since the ions don’t escape mucous builds up on the outside of the CFTR which is hard to clear and is a good media for bacteria growth.
Cytoskeleton
The cytoskeleton is a mesh work of protein rods and tubules
Function: Maintain cell shape, connect cells to each other, transport organelles and small molecules, provide cell motility, move chromosomes in cell division, and compose cilia
Microtubules: Biggest diameter, made up of the protein tubulin, they also form cilia move chromosomes during mitosis/meiosis (uniformly throughout, the railroads)
Microfilaments: Smallest diameter, made up of actin protein, involved in stretching and anchoring the cells (on the cell membrane)
Intermediate Filaments: Medium diameter, made up of multiple proteins, and is abundant in skin and nerve cells
Hereditary Spherocytosis
Summary: the spleen is suppposed to get rid of RBCs but during Hereditary Spherocytosis it does not. Due to a mutation in the cytoskeleton, the RBCs are a different shape, and this causes the spleen to get rid of all the RBCs (anemia). The symptoms of anemia is fatigue, poor growth, and icky feeling. Ankyrin is what causes the microfilaments to connect to the cell membrane, but in hereditary Spherocytosis there’s an abnormality of the ankyrin. Most infected people are heterozygous because it is an autosomal dominant disease. The most common treatment is blood transfusion.
Signal Transduction
Summary: A cell gets a stimulus that causes the cell to react and pass that signal through the cell membrane until it reaches an enzyme that creates a reaction. This creates cAMP or the second message which responds and amplifies the stimulus. The response could be movement, cell division, secretion, or metabolic change.
Steps:
1. Stimulus (light, chemical gradient, temperature change, toxin, hormone, growth factor, etc.) binds w/ receptor
2. This interacts and sends a signal to a regulatory protein
3. The regulatory proteins sends a signal to an enzyme
4. The enzyme then amplifies the message the the use of cAMP.
Neurofibromatosis 1
One of the most common genetic disorder, caused by an abnormality w/ signal transduction
7 Clinical Features (2 Required for Diagnosis):
1. A first-degree relative w/ NF1
2. Six or more cafe au last maculae’s over 5 mm in diameter (looks like birthmarks)
3. 2 or more neurofibromas of any type or one plexiform neurofibroma
4. Freckling in the axillary or in Guiana regions
5. Optic glioma
6. Two or more Lisch nodules
7. A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis.
Cause: due to mutations in the NF1 Gene. It affects 1/3,000 births. Cafe au last macules are commonly the first sign. Patient w/ NF require frequent monitoring for complications. NF1 gene encodes the protein neurofibromin. Neurofribromin is part of a signal transduction cascade that controls cellular proliferation. The mutated NF1 results in increased cellular proliferation.
Interphase
G1: (after cytokinesis) cell resumes synthesis of proteins, lipids, and carbohydrates: building blocks for plasma membrane. Cells may exit G1 to G0 in slowly dividing tissues. Some cells can stay in G0 for years or life, and other may skip G1 entirely
S: Cell replicates its entire genome, last 8-10 hours
G2: Protein synthesis again, membranes are made from the proteins in G1.
Mitosis
Lasts 1-2 hours, results in one chromatid of each number to each daughter cell, and chromosomes segregation
Prophase: Replicated chromosomes condense, microtubules organize into spindle, and nuclear envelop and nucleus break down.
Metaphase: Spindle and microtubules are attached to centromeres of chromosomes, chromosomes line up on the equator, chromosomes maximally condense
Anaphase: Centromeres divide, chromatids separate, they move to opposite ends of the cell, plasma membrane begins to indent via the microfilaments
Telophase: Chromosomes uncoil, spindle disassembles, nuclear envelope and nucleolus reforms.
Cytokinesis
Cytoplasmic division occurs after nuclear division is complete, organelles and macromolecules are distributed between the two daughter cells, and microfilaments band contracts separating the two cells.
Cell Checkpoints
Apoptosis Checkpoint: Between G2 and M phase, throughout interphase the protein survivin accumulates and if there’s enough it makes it past this checkpoint
DNA Damage Checkpoint: During S phase, checks to see if the DNA is damaged during replication, if so it fixes it
Spindle Assembly Checkpoint: between metaphase and anaphase, makes sure mitosis spindle is built correctly
Telomeres
Summary: Contain 100-1,000 repeats of a 6-base DNA sequence (TTAGGG), most cells lose 50-200 endmost bases after each cell division, after about 50 divisions the shortened telomeres signal the cell to stop dividing, sperm eggs bone marrow and cancer cells produce telomerase that prevent the shortening of telomeres
Function: Prevent fraying because frayed ends could be attacked by enzymes and shorten the DNA, allow the replication machine to continue the end of the DNA, and fold into a looped structure and associate proteins to form a cap
Location: End of chromosomes
Dyskeratosis Congenita
Classic Triad of Symptoms: dysplastic fingernails, lacy pigmentation of upper chest/neck, and oral leukoplakia (whiteness in mouth)
Increased risk: progressive bone marrow failure, myelodysplastic syndrome (MPS) or acute myelogenous leukemia (AML), solid tumor and pulmonary fibrosis
Diagnosis: shortened telomeres
Genes Responsible: DKC1, TERC, TERT, TINF2, NHP2, NOP10
Inheritance: Autosomal Recessive, autosomal dominant, and x-linked
Molecular Genetics: TERT - a reverse transcriptase that is responsible for adding the TTAGGG, other proteins stabilize looped complex/cap
Other Factors Affecting Cell Cycle
Environment: environmental stress may accelerate telomere shortening
Space: crowding halts mitosis
Chemical Signs: hormones and growth factors influence mitotic rate
Proteins: cyclins and kinases interact to activate the genes to carry out mitosis
Apoptosis
Killer enzymes called caspases destroy cellular components, dying cells forms bulges called bless, the nucleus bursts and DNA is released, mitochondria decompose preventing energy utilization, the cell shatters into fragments, and fragments are phagocytized to prevent inflammation.
Meiosis
Cell division that produces gametes w/ half the number of chromosomes, occurs in the ovaries and testes maintains the chromosome number of a species over generations, and ensure genetic variation via the process of independent assortment and crossing over of chromosomes.
Consists of two parts:
Meiosis 1: 46 to 23 chromosomes
Meiosis 2: Produces the final four haploid cells
Results:
Four haploid cells containing a single copy of the genome, each cell is unique
Prophase 1
Homologous pair-up and undergo crossing over, chromosomes condense, spindle forms, nuclear envelope breaks down
Pachytene: part of prophase 1, where crossing over occurs
Crossing-Over (Recombination)
Summary: One sister chromatid involved in each crossover event, >= 1 chiasmata per chromosome arm for normal segregation, the number of chiasmata correlates w/ the length of the arm, failure to recombine properly can lead to abnormal segregation of chromosomes in meiosis 1
Synaptonemal Complex: association of chromosomes before crossing over which is mediated by proteins
Chiasmata: the location of crossover events
Metaphase 1
Summary: Homologous pairs align along the equator of the cell, random alignment pattern determines the combination of maternal and paternal chromosomes in the gametes, and independent assortment occurs here.
Independent Assortment
Mendelian idea; the rule that each individual chromosome (ex. Chromosome 1) will line up independently of the other chromosomes (ex. Chromosome 2-23) during metaphase 1.
Anaphase 1
Homologs separate and move to opposite poles of the cell, sister chromatids remain attached at their centromeres.
Telophase 1
Nuclear envelope reforms, spindle disappears, then cytokinesis happens diving the one cell into two new ones.
Interkinesis
A short interphase between the two meiosis divisions, chromosomes unfold into very thin threads, proteins are manufactured, however DNA is not replicated a second time.
Prophase 2
Chromosomes condense and become visible, spindle forms, and nuclear envelope fragments
Metaphase
Chromosomes align along the equator of the cell
Anaphase 2
Centromeres divide, sister chromatids separate to opposite cell poles.
Telophase 2
Nuclear envelope reforms, chromosomes uncoil, and spindle disappears
Spermatogenesis
Males start making sperm during puberty, and they continue making sperm for the rest of their life.
This is considered continuous
Mitosis and Meiosis occur in the testes.
Mitosis occurs to make more cells that will eventually become sperm (called spermatogonium)
Spermatogenesis occurs in the seminiferous tubule in the testes. The 4 sperm travel w/ each other and then get released at the same time.
Oogenesis
Females start oogenesis before birth; all eggs are made before birth but aren’t active until puberty
This is considered a discontinuous process
Oogonium does mitosis then meiosis 1 and 2. Only one mature egg results from this process. The other 3 are polar bodies that are recycled by the body
2 Arrests:
1. Occurs in Prophase 1, specifically the dictyotene period, where the egg will be held until ovulation
2. Occurs in Metaphase 2, at the time of mestruation a cell is taken from dictyotene to metaphase 2, metaphase 2 is never completed unless the cell is fertilized, and fertilization takes place in the fallopian tubes
The first polar body is found after Telophase 1, and the next one occurs at Telophase 2. Since the egg only gets pass Metaphase 2 metaphase 2, the second polar body rarely occurs. We can get genetic information from the second polar body. Sometimes 2 egg cells are ovulated during the menstruation cycle.
Fertilization
The sperm crosses the corona radiata (a layer of protective cells that surround the egg). The corona radiata also allaows only one sperm to get into the egg. The sperm then has to fuse w/ the nucleus of the egg.
