Genetics
· Chromosomes
o Genes are in side the chromosomes
o Human have 46 chromosomes, in 23 pairs.
§ 22 of the pairs are called autosomes.
· All of the genes in these control traits that are not related to gender.
§ 1 pair is called the sex chromosomes.
· Contains the genes that control gender
o Males have XY chromosomes.
o Females have XX chromosomes.
o Every cell except red blood cells contains chromosomes.
o When a cell divides chromatin become chromosomes, the nuclear envelope fragments to release the chromosomes.
· Cell Cycle
o A process that has 2 parts:
§ Interphase: Part One
· 90% of the cell cycle
· 3 stages:
o G1 Stage:
§ Organelles and chromatin double.
§ Materials needed for DNA synthesis accumulate.
§ Proteins needed to transform chromatin into chromosomes are gathered.
o S Stage:
§ DNA replication occurs.
§ DNA replication results in duplicated chromosomes.
§ Each chromosome consists of 2 identical DNA double helix molecules.
o G2 Stage:
§ The cell synthesizes the cell needed for cell division.
§ Cell Division: Part Two
· 2 Stages:
o M-Mitotic
§ Sister chromatids of each chromosome separate becoming chromosomes that are distributed to two daughter nuclei.
o Cytokinesis
§ Division of the cytoplasm
·Phases of Mitosiso 4 Stages:
§ Prophase
· Centrosomes outside nucleus duplicate and move to opposite ends of the nucleus.
· Spindle fibers appear between the separating centrosomes
· The nuclear envelope begins to fragment.
· The nucleolus disappears as the chromosomes coil and become condensed.
· Chromosomes become visible, consisting of two sister chromatids held together at the centromere.
· Spindle Fibers attach to the centromeres as the chromosomes continue to shorten and thicken.
· During this phase chromosomes are randomly placed in the nucleus.
§ Metaphase
· The nuclear envelope completely fragments.
· The spindle is where the nucleus used to be.
· Chromosomes are at the center of the spindle.
· The spindle is fully formed during the phase.
§ Anaphase
· The centromeres holding the sister chromatids divide, separating the sister chromatids where they turn into chromosomes.
· The chromosomes move towards opposite ends of the spindle.
· Each pole receives the same number of chromosomes.
§ Telophase
· Starts when chromosomes arrive at the poles of the spindle.
· The chromosomes become indistinct chromatin again.
· The spindle disappears and the nuclear reassembles in each cell.
· This phase is characterized by the presence of 2 daughter nuclei.
· Cytokinesis
o The division of the cytoplasm and organelles.
o A slight indentation called a cleavage furrow passes around the outside of the cell.
o Actin filaments form a contractile ring.
o As the ring gets smaller the cleavage furrow pinches the cell in half.
o This process causes each cell to be enclosed by its own plasma membrane.
· Meiosis
o 2 Stages of Cell Division:
§ Meiosis I
· Homologous chromosomes come together and line up side by side (synopsis)
o Homologous chromosomes are pairs of chromosomes that look alike and carry genes for the same traits.
· This creates pairs of homologous chromosomes at the center of the spindle.
§ Meiosis II
· Centromeres divide and sister chromatids separate, becoming chromosomes that are distributed to daughter nuclei.
· The daughter cells mature into gametes that fuse during fertilization.
o Gametes: sex cells: sperm and eggs.
· Fertilization restores the diploid number of chromosomes in the zygote.
o Stages of meiosis
§ Meiosis I and Meiosis II, both have the same 4 stages of nuclear division as Mitosis.
o Prophase
o Metaphase
o Anaphase
o Telophase
o Significance of Meiosis
§ It is a part of gameogenesis, the production of the sperm and egg.
§ To keep the chromosome number constant from generation to generation.
§ The process results in genetic recombination, which ensures that offspring will be genetically different.
· Comparison of Meiosis and Mitosis
o Meiosis requires 2 nuclear divisions. Mitosis requires 1 nuclear division.
o Meiosis produces 4 daughter nuclei and following Cytokinesis there are 4 daughter cells. Mitosis results in 2 daughter cells.
o In meiosis 4 daughter cells are haploid and have half the chromosome number of the parent cell. In mitosis daughter cells have the same number of chromosomes as the parent cell (diploid).
o In meiosis daughter cells are not genetically identical to each other or to the parent cell. In mitosis the daughter cells are identical to each other and the parent cell.
o Meiosis occurs in the reproductive organs. Mitosis occurs in all tissue types during growth and repair.
· Spermatogenesis
o Is the production of sperm in males.
o All four daughter cells become sperm. Sperm has 23 chromosomes (the haploid number).
· Oogenesis
o Is the production of eggs in females.
· Chromosome Inheritance
o Normally an individual receives 22 pairs of autosomes and 2 sex chromosomes.
o Each pair of autosomes carries alleles for certain traits, the alleles can be different.
o Sometimes individuals are born with too many or too few autosomes or sex chromosomes.
§ This will usually happen during meiosis due to nondisjunction.
· Nondisjunction
o Occurs during meiosis I when both members of a homologous pair go into the same daughter cell.
o Or in meiosis II when a sister chromatin fails to separate and both daughter chromosomes go into the same gamete.
o It may occur during Oogenesis
o Normal development requires 2 kinds of each chromosome.
o Example of different chromosomal abnormalities
§ Down Syndrome
· Autosomal Trisomy
· Most common
· There will usually be 3 copies of chromosome 21.
· Karotyping is able to detect the defect.
· The genes that cause it are located on the bottom 3rd of chromosome 21.
§ Changes in sex chromosome #
· Results from inheriting too many or too few X or Y-chromosomes.
o Turner Syndrome (XO)
§ Has only 1 sex chromosome (X)
§ Persons do not go through puberty
§ Persons are of normal intelligence
o Klinefelter Syndrome (XXY)
§ Symptoms are very subtle
§ Speech and language delays
§ Will require assisted reproduction to father children
§ Receive testosterone supplementation at the start of puberty
o Poly X Female (XXX)
§ Has more than two X chromosomes and has extra barr bodies in the nucleus.
§ Tendency to be tall and thin
§ Delayed motor and language development.
o Jacobs Syndrome (XYY males)
§ Results from nondisjunction during spermatogenesis.
§ Taller than average
§ Persistent acne
§ Speech and reading problems.
· Changes in Chromosome structure
o Another type of chromosomes mutation when the chromosomes “break” and do not rejoin in the same pattern.
o Types include:
§ Deletion: the loss of a chromosomes piece.
§ Duplication: when a chromosomal segment is repeated in the same chromosome.
§ Inversion: when a piece of chromosome breaks loose and then rejoins in the reversed direction.
§ Translocation: the exchange of chromosome pieces between nonhomologous pairs.
o Human Syndromes
§ Deletion Syndromes
· Williams Syndromes
o Chromosome 7 loses a tiny end piece.
· Cru du chat (cats Cry)
o Chromosome 5 is missing an end piece.
· Translocation Syndromes
o The chromosome exchange breaks an allele into 2 piece; causing 1 of the translocated chromosomes to have only 1 copy of certain alleles and 3 copies of certain other alleles.
- DNA and RNA Structure and Function
- Structure of DNA
- Double helix, 2 strands that spiral.
- Each strand is a polynucleotide
- Polynucleotide: molecule of 3 subunits
- Phosphoric acid ( Phosphate)
- Pentose sugar (deoxyribose)
- Nitrogen containing base
- Phosphate- Sugar backbones are the support of the ladder.
- Paired Bases are the rungs held together by hydrogen bond.
- Replication of DNA
- The process of copying a DNA Helix.
- Before replication, the 2 strands that make up parental DNA are hydrogen bonded together.
- An enzyme “un zips” the double stranded DNA.
- New complimentary DNA nucleotides (always present in the nucleus) fit into place through complimentary base pairing.
- An enzyme seals any breaks in the phosphate-sugar backbone.
- The 2 double-helix molecules are identical to each other and to the original DNA molecule.
- A replication error that persists is a mutation
- Mutation: permanent change in the sequence of bases that may cause a change in the phenotype and introduce variability. The variability’s are what make you different.
- Structure and Function of RNA
- RNA is made of nucleotides containing the sugar ribose.
- Is single stranded
- In place of base thymine is uracil.
- Helper to DNA, allowing protein synthesis to occur according to the stored genetic information provided by DNA.
- Three types of RNA
- rRNA (ribosomal RNA)
- Joins with proteins made in the cytoplasm to form the subunits of ribosomes.
- mRNA (messenger RNA)
- Carries genetic information from DNA to ribosomes in the cytoplasm where protein synthesis occurs.
- tRNA (transfer RNA)
- Transfers amino acids to the ribosomes, where the amino acids are joined, forming a protein.
- Gene expression
- 2 Steps
- Transcription
- Translation
- Is possible only if the bases in DNA and mRNA code for amino acids, called genetic code.
- Genetic Code
- 4 bases stand for 1 amino acid
- Supplies 64 different triplets
- Each 3 letter unit of an mRNA molecule is a codon
- 61 triples correspond to a particular amino acid, remaining 3 are stop-codons which signal polypeptide termination.
- Transcription
- Occurs in the nucleus
- The DNA Helix opens to make a template.
- The mRNA transcript is made from the DNA template
- Translation
- Occurs outside the nucleus.
- The ribosomes do the translation.
- They glom onto mRNA and line up amino acids in a chain (polypeptide chain) according to mRNA sequence.
- Regulation of Gene Expression
- Cells differ by which genes are expressed.
- 4 primary levels of control
- Transcriptional Control
- In the nucleus
- The organization of chromatin and use of transcription factors that start transcription regulate gene transcription.
- Post Transcriptional Control
- In the nucleus
- The amount of the gene expressed is controlled by how fast mature mRNA leaves the nucleus.
- Translational Control
- In the cytoplasm
- Occurs after mRNA leaves nucleus and before there is a protein product.
- Post Translational Control
- In the cytoplasm
- Occurs after protein synthesis.
- Characteristics of Cancer Cells
· They lack differentiation
o Cells are non-specialized, they do not contribute to the functioning of body parts
o They look distinctly different.
· Abnormal Nuclei
o The nuclei are enlarged.
o It may have an abnormal number of chromosomes.
o The chromosomes are abnormal.
§ Portions may be deleted or duplicated
§ Gene amplification occurs (extra copies of specific genes)
o They do not go through aptopsis-programmed cell death.
· Unlimited Replicative Potential
o Cells are immortal and keep on dividing for an unlimited number of times (normal cells divide 60-70 times then die)
o The gene that codes for telomerase is turned on.
§ Telomerase: continually rebuilds the telomeres in cancer cells, remaining at a constant length (normal cells get shorter after each division and eventually die).
· Form Tumors
o Cells pile on top of one another and grow in multiple layers forming a tumor.
o Benign tumor- is encapsulated and will never invade adjacent tissues.
· No need for growth factors
o Cells divide when the stimulatory growth factors are not present.
o Cells do not respond to inhibitory growth factors.
· Cells gradually become abnormal
o Carcinogenesis- the development of Cancer
o 3 phases
§ Initiation: the cell undergoes mutation, causing it to divide repeatedly
§ Promotion: the tumor develops; tumor cells continue to divide, undergoing mutations.
§ Progression: One cell mutates to give it a selective advantage over other cells; the process is repeated giving the cells the ability to invade surrounding tissues.
· Undergo Angiogenesis and Metastasis
o Angiogenesis: formation of new blood vessels
§ Brings the tumor nutrients and oxygen to grow.
o Metastasis: is when cancer cells found in nearby lymphnodes, causes new tumors far from the 1st tumor.
· Cancer is a Genetic Disease
o Repeated cell cycles are caused by mutation of 2 types of genes.
§ Proto-oncogenes: code for proteins that promote the cell cycle and prevent apoptosis.
§ Tumor-suppressor genes- code for proteins that inhibit the cell cycle and promote apoptosis.
o Proto-Oncogenes -Oncogenes
§ Proto-oncogenes turn into oncogenes
§ Oncogenes are the result of mutation of proto-oncogenes.
§ Oncogenes are an over functioning proto-oncogene.
§ A gain of function mutation
o Tumor Suppressor Gene becomes inactive
§ Mutations cause the gene to no longer inhibit the cell cycle nor promote apoptosis.
§ Loss of function mutation
· Types of Cancer
o Oncology is the study of cancer.
o Tumors are classified according to place of origin.
§ Carcinomas- in the epithelial tissue
§ Sarcomas- in the muscle and connective tissue.
§ Leukemia’s- in the blood.
§ Lymphomas- in the lymphatic tissue.
· Causes of cancer
o Causes
§ Heredity
§ Environmental Carcinogens
· Radiation
o Uv light
o Radon gas
o X-rays
o Nuclear fuel
· Organic chemicals
o Tobacco smoke
o Pollutants
§ Asbestos, nickel, cadmium, uranium
· Viruses
o Hepatitis B and C
o Epstein-Barr Virus
o Human Papillomavirus
o Diagnosis of Cancer
§ Seven warning signs
· Change in bowel of bladder habits
· A sore that does not heal
· Unusual bleeding of discharge
· Thickening or lump in breast or other places
· Indigestion or difficulty swallowing
· Obvious change in wart or mole
· Nagging cough or hoarseness
§ Routine screening tests
· Self-examination followed by physician examination
· ABCD’s of melanoma
o A- Asymmetry, one half of mole does not look like the other half.
o B- Border, irregular scalloped or poorly circumscribed border.
o C- Color, varied from one area to another; shades of tan, brown, black, or sometimes white, red, or blue.
o D- Diameter, larger than 6mm.
· Tumor marker test
o Blood test for tumor antigens/ antibodies
· Genetic Tests
o Testing for genetic mutations in proto-oncogenes and tumor suppressor genes.
o Treatments of cancer
§ Surgery- for a specific location
§ Radiation Therapy- for a specific location
§ Chemotherapy- for the entire body
§ Bone Marrow Transplants
§ Genotypes and Phenotypes
o Genotype
§ Alleles: the alternative forms of a gene having the same position (Locus) on a pair of chromosomes and affecting the same trait.
§ Dominant allele: is assigned a upper case letter
§ Recessive Allele: assigned a lower case letter.
§ Occur in pairs, two alleles per trait
§ One of each pair of alleles is inherited from each parent.
§ Homozygous Dominant: 2 dominant alleles
§ Homozygous Recessive: 2 recessive alleles
§ Heterozygous: 1 dominant 1 recessive allele
o Phenotype
§ The physical appearance of the individual
§ Can be any characteristic of the individual.
§ One- and Two- Trait Inheritance
o One-Trait Crosses
§ The inheritance of only one set of alleles
o Two-Trait Crosses
§ The inheritance of two sets of alleles
o For both types of crosses it is necessary to determine the gametes of both parents.
§ Forming the Gametes
o Gametes are the same as alleles
o Gametes can carry one allele for each trait
o If an individual carries alleles “EE” all the gametes will carry an E
o If an individual carries an “Ee” half the gametes will carry an “E” and half will carry an “e”.
§ Autosomal Recessive Disorder
o Inheritance of 2 recessive alleles is required before the disorder will appear.
§ Autosomal Dominant Disorders
o Inheritance of only 1 dominant allele is necessary for the disorder to appear.
§ Beyond simple Inheritance Patterns
o In some patterns of inheritance the alleles are not just dominant or recessive.
o Polygenic inheritance
§ Polygenic traits are controlled by more than one set of alleles. The dominant alleles have an additive effect on the phenotype.
o Incomplete Dominance and Codominance
§ Incomplete Dominance: the heterozygote is intermediate between the 2 homozygotes
§ Codominance: both dominant alleles are expressed equally.
§ Multiple Allele Inheritance
o Every individual has 2 out of 3 possible alleles
No comments:
Post a Comment