Genetics
Four types of nitrogen bases
Four types of nitrogen bases(T) pairs with (A)(G) pairs with (C)
A Adenine (T) Thymine(G) Guanine(C) Cytosine
A and G are purines and T and C are pyrimidine
Mutation – A change to a DNA sequence or gene.Causes – Chemicals, Radiation, UV Rays
Translation – The process of translating the sequence of messenger RNA molecule to a sequence of amino acids during protein synthesis
Transcription – The synthesis of RNA from DNA template
Replication – Whenever a cell divides, the two daughter cells must have the same genetic information.
Pedigree Analysis – A tabular representation of family history by taking a particular disease or character into consideration.
Humans have 23 pairs (46) of chromosomes. The 23rd pair is called sex chromosome.
Male = XY chromosomesFemale = XX chromosomes
Protein synthesis in a cell: Has two steps Transcription and Translation
Transcription; process of DNA -> messenger RNA (mRNA), has 3 steps (Initiation, elongation and termination)
Translation; mRNA to Protein
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Mitosis – Eukaryotic cell division in which two daughter cells are produced with the same genetic component as the parent cell
Prophase occupies over half of mitosis. The nuclear membrane breaks down to form a number of small vesicles and the nucleolus disintegrates. A structure known as the centrosome duplicates itself to form two daughter centrosomes that migrate to opposite ends of the cell. The centrosomes organise the production of microtubules that form the spindle fibres that constitute the mitotic spindle. The chromosomes condense into compact structures. Each replicated chromosome can now be seen to consist of two identical chromatids (or sister chromatids) held together by a structure known as the centromere.
Prometaphase The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid-line of the cell – at right-angles to the axis formed by the centrosomes. This region of the mitotic spindle is known as the metaphase plate. The spindle fibres bind to a structure associated with the centromere of each chromosome called a kinetochore. Individual spindle fibres bind to a kinetochore structure on each side of the centromere. The chromosomes continue to condense.
Metaphase The chromosomes align themselves along the metaphase plate of the spindle apparatus.
Anaphase The shortest stage of mitosis. The centromeres divide, and the sister chromatids of each chromosome are pulled apart – or ‘disjoin’ – and move to the opposite ends of the cell, pulled by spindle fibres attached to the kinetochore regions. The separated sister chromatids are now referred to as daughter chromosomes. (It is the alignment and separation in metaphase and anaphase that is important in ensuring that each daughter cell receives a copy of every chromosome.)
Telophase The final stage of mitosis, and a reversal of many of the processes observed during prophase. The nuclear membrane reforms around the chromosomes grouped at either pole of the cell, the chromosomes uncoil and become diffuse, and the spindle fibres disappear.
Cytokinesis The final cellular division to form two new cells. In plants a cell plate forms along the line of the metaphase plate; in animals there is a constriction of the cytoplasm. The cell then enters interphase – the interval between mitotic divisions.
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Meiosis – Meiosis is the form of eukaryotic cell division that produces haploid sex cells or gametes (which contain a single copy of each chromosome) from diploid cells (which contain two copies of each chromosome).
Meiosis I –
Prophase 1. • As in mitosis, the nuclear membrane dissolves, chromosomes develop from the chromatin, and the centrosomes push apart, creating the spindle apparatus. • The tight pairing of the homologous chromosomes is called synapsis • These paired up chromosomes—two from each parent—are called tetrads. • The point the points of contact, the physical link, between two (non-sister) chromatids belonging to homologous chromosomes is the chiasmata • Homologous (similar) chromosomes from both parents pair up and may exchange DNA in a process known as crossing over. This results in genetic diversity. •
metaphase 1, some of the spindle fibers attach to the chromosomes’ centromeres. • The fibers pull the tetrads into a vertical line along the center of the cell.
Anaphase 1 is when the tetrads are pulled apart from each other, with half the pairs going to one side of the cell and the other half going to the opposite side. • It is important to understand that whole chromosomes are moving in this process, not chromatids, as is the case in mitosis.
• At some point between the end of anaphase 1 and the developments of telophase 1, cytokinesis begins splitting the cell into two daughter cells. • In telophase 1, the spindle apparatus dissolves, and nuclear membranes develop around the chromosomes that are now found at opposite sides of the parent cell / new cells,
Meiosis II –
In prophase 2, centrosomes form and push apart in the two new cells. • A spindle apparatus develops, and the cells’ nuclear membranes dissolve. • Spindle fibers connect to chromosome centromeres in metaphase 2 and line the chromosomes up along the cell equator.
During anaphase 2, the chromosomes’ centromeres break, and the spindle fibers pull the chromatids apart. •
The two split portions of the cells are officially known as “sister chromosomes” at this point. As in telophase 1, telophase 2 is aided by cytokinesis, which splits both cells yet • resulting in four haploid cells called gametes. Nuclear membranes develop in these cells, which again enter their own interphases.
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Transcription is the process of transcribing DNA into mRNA so that it can be translated into proteins. It is also the first major step of gene expression. Transcription produces a complimentary sequence to the DNA; A bonds with T in DNA, U bonds with A, G bonds with C and C bonds with G.
Initiation
Activator proteins bind to distal control elements that are located before the DNA sequence known as a promoter. Promoters are located near the start sites of genes, and allow various proteins and enzymes (such as RNA polymerase II) to form an initiation complex that begins transcription.
Proteins called transcription factors bind to a specific DNA sequence known as a promoter. At this point in the process, the DNA is still double stranded. RNA polymerase binds to the promoter region shortly after the transcription factors.
RNA polymerase unwinds approximately 14 base pairs to form an “open complex” that becomes the transcription bubble. As the RNA polymerase begins creating RNA, it enters the RNA exit channel and leaves behind the initial transcription factors.
Elongation
RNA polymerase begins unwinding the double helix and exposes 10-20 nucleotides for transcription at a time. To do this, RNA polymerase uses free-floating RNA nucleotides in the nucleoplasm.
RNA polymerase travels from the 3′ → 5′ direction on the template strand of DNA, producing a mRNA strand in the 5′ → 3′ direction. This process produces an RNA copy of the 5′ → 3′ strand of DNA.
RNA transcription occurs very quickly, and can involve multiple RNA polymerase working on a single gene. The typical rate of elongation is 10-100 nucleotides/sec.
Elongation also involves a proofreading mechanism that can replace incorrect nucleotides. Transcription pauses, allowing RNA editing factors to bind to the new strand of mRNA and edit base order.
Termination
The RNA codes for thepolyadenylationn (AAUAAA), and the proteins that have been associated with the RNA polymerase stop moving.
RNA polymerase continues moving, adding hundreds of adenine nucleotides to the end of the mRNA strand. Spare RNA created like this may be used by enzymes.
This termination factor releases the newly created mRNA, which leaves the nucleus and travels to the ribosome where it is translated into a protein.
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Translation is the process of translating the mRNA created during transcription into a protein. These proteins are responsible for different genetic traits such as hair/eye color, blood type, or hereditary conditions such as color blindness. It takes place in the ribosome, an organelle with three chambers and two subunits that consists of rRNA and other proteins. The three chambers are the A site (Aminoacyl-tRNA binding site), the P site (Peptidyl-tRNA binding site) and the E site (Exit site). All of these chambers are located in the large subunit. Like transcription, it occurs in three steps.
Initiation
The small subunit attaches to the mRNA, holding it in place throughout translation.
The Methionine tRNA bonds to the start codon AUG.
The large subunit arrives and completes the translation initiation complex.
Elongation
Amino acids are brought to the ribosome by tRNA molecules and are added to the polypeptide chain one by one.
The anticodon on a tRNA molecule binds to the mRNA codon at the A site.
An rRNA molecule in the large subunit catalyzes the formation of a peptide bond between the amino acid on the tRNA and the polypeptide chain.
The ribosome moves the mRNA to from the P site to the E site, where the tRNA is released.
Termination
The stop codon on the mRNA reaches the A site.
Release factors bind to the stop codon at the A site.
A water molecule is added to the end of the polypeptide instead of an amino acid, and hydrolysis releases the chain so it can be folded into its final structure.
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Replication
Initiation –Replication begins at a location on the double helix known as “oriC” to which certain initiator proteins bind and trigger unwinding. Enzymes known as helicases unwind the double helix by breaking the hydrogen bonds between complementary base pairs, while other proteins keep the single strands from rejoining. The “topoisomerase” proteins surround the unzipping strands and relax the twisting that might damage the unwinding DNA. The cell prepares for the next step, elongation, by creating short sequences of RNA called primers that provide a starting point of elongation.
Elongation- With the primer as the starting point for the leading strand, a new DNA strand grows one base at a time. The existing strand is a template for the new strand. For example, if the next base on the existing strand is an A, the new strand receives a T. The enzyme DNA polymerase controls elongation, which can occur only in the leading direction. The lagging strand unwinds in small sections that DNA polymerase replicates in the leading direction. The resulting small “Okazaki fragments” can contain 1,000 to 2,000 bases in bacteria, but eukaryotes — organisms having cells with nuclei — have fragments of only 100 to 200 bases. The fragments terminate in an RNA primer that is subsequently removed so that enzymes can stitch the fragments into an elongating strand.
Termination- After elongation is complete, two new double helices have replaced the original helix. During termination, the last primer sequence must be removed from the end of the lagging strand. This last portion of the lagging strand is the telomere section, containing a repeating non-coding sequence of bases. Enzymes snip off a telomere at the end of each replication, leading to shorter strands after each cycle. Finally, enzymes called nucleases “proofread” the new double helix structures and remove mispaired bases. DNA polymerase then fills in the gaps created by the excised bases.
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Difference Between Heterochromatin and Euchromatin
Heterochromatin is a part of chromosome, a tightly packed form of DNA whereas euchromatin is an uncoiled form of chromatin.
• Heterochromatin has tighter DNA packing than euchromatin.
• Heterochromatin stains dark in interphase whereas euchromatin stains lightly with basic dyes but stains dark during mitosis, when it is in condensed state during each repetition of the cell cycle.
• Heterochromatin contains more number of DNA compare to euchromatin.
• Heterochromatin found in eukaryotes whereas euchromatin found in both eukaryotes and prokaryotes.
• Heterochromatin is genetically inactive and euchromatin is genetically active.
• Heterochromatin is late replicative whereas euchromatin is early replicative.
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Genetic Disorders
• Causes of mutations – chemicals, radiation, temperature, viruses
• Nondisjunction – chromatids do not separate properly during meiosis. Individual formed from such gametes have extra or missing chromosomes. as Down’s Syndrome
• Trinucleotide repeats – sequences of 3 nucleotides is repeated, often several times in a gene when too many repeats are formed – cause genetic disorders triplet nucleotides -repeated too often as Huntington’s • Defective genes – does not produce correct protein as sickle cell anemia (A & T traded places)
• Genetic disorders and their causes
• Human genetic disorders – can be dominant, recessive, sex-linked, epistatic, variable expressed
• Crossover frequency – during meiosis, pieces trade places – determining frequency
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ZYGOSITY: Zygosity refers to the grade of similarity between the alleles that determine one specific trait in an organism. In its simplest form, a pair of alleles can be either homozygous or heterozygous. Homozygosity, with homo relating to same while zygous pertains to a zygote, is seen when a combination of either two dominant or two recessive alleles code for the same trait. For example, using ‘A’ as the representative character for each allele, a homozygous dominant pair’s genotype would be depicted as ‘AA’, while homozygous recessive is shown as ‘aa’. Heterozygosity, with hetero associated with different, can only be ‘Aa’ because ‘aA’ is not biologically correct. The phenotype of a homozygous dominant pair is ‘A’, or dominant, while the opposite is true for homozygous recessive. Heterozygous pairs always have a dominant phenotype.[2] To a lesser degree, hemizygosity[3] and nullizygosity[4] can also be seen in gene pairs.
DNA mutation
– Is a change in DNA, can cause changes in all aspects of its life
-Types of mutations: Substitution, insertion, deletion, frameshift
Substitution: One base exchanges for another
Insertion: Extra base pairs are added
Deletion: Sections of DNA are lost
Frameshift: Alterations of a gene so that its message is unclear
Sex Linked Traits: VuforiaLocalizer vuforia = ClassFactory.getInstance().create Vuforia(parameters);
Definition: A trait associated with a gene that is carried only by the male or female parent
X linked traits recessive and dominant: X-linked traits means that they are expressed on the x chromosome. … Hence, to answer the question, an X-linked
dominant trait is a dominant characteristic located in the x chromosome, while an X-linked recessive trait is one that is recessive and located in the same
Chromosome
Gene Expression:Gene expression is the process by which the heritable information in a gene, the sequence of DNA base pairs, is
made into a functional gene product, such as protein or RNA. DNA is transcribed into RNA, which is then translated into proteins.
Genes encode proteins and proteins dictate cell function. Therefore, the thousands of genes expressed in a particular cell
determine what that cell can do. Moreover, each step in the flow of information from DNA to RNA to protein provides the cell with a
potential control point for self-regulating its functions by adjusting the amount and type of proteins it manufactures.
Epistasis and multifactorial inheritance
Multifactorial Inheritance: Multifactorial inheritance means that many factors are involved in causing a birth defect.
The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown
environmental factors, produce the trait or condition.
Epistasis: The interaction between two or more genes to control a single phenotype so one pair of genes alters the expression of
another pair of genes
Genetic Variations: Probability – ratios or percentages Multiple Alleles – three or more alleles for a gene as blood type as skin color Multifactorial Traits –
more than 1 pair of genes plus environment Pleiotropy – the action of an allele (gene) affects many parts of the body as sickle cell anemia Variable
Expressivity – an allele (gene) can be expressed differently in different people
Sex Linkage: Sex linkage is the phenotypic expression of an allele that is dependent on the gender of the individual and is directly tied to the sex chromosomes. In
such cases there is a homogametic sex and a heterogametic sex In such cases there is a homogametic sex and a heterogametic sex.In mammals the homogametic
sex is female (XX) and the heterogametic sex is male (XY), thus the sex linked genes are carried on the X chromosome. In birds and in some insects the
homogametic sex is male.Homogametic sex- The sex that is determined by possession of two similar sex chromosomes (e.g. XX). In humans and many other
mammals this is the female sex.Heterogametic sex (digametic sex) refers to the sex of a species in which the sex
chromosomes are not the same. For example, in humans, males, with an X and a Y sex chromosome, would be
referred to as the heterogametic sex.
Lethal Genes- a gene that is capable of causing the death of an organism, usually during the development of the embryo.
Difference between mitosis and meiosis: Mitosis is responsible for reproducing somatic cells and meiosis is responsible
for reproducing germ cells.
Trisomy-a condition in which an extra copy of a chromosome is present in the cell nuclei, causing abnormalities
Monosomy- a single copy of a chromosome pair instead of the usual 2 copies
Translocation-a type of chromosome abnormality in which the chromosome breaks and a portion reattaches to a different chromosome
Deletion-a type of mutation involving the loss of genetic material
Inversion- a single chromosome undergoes breakage and rearrangement within itself
Law of Dominance – An organism with alternate forms of a gene will express the form that is dominant.
Law of Independent assortment – Genes for different traits are sorted separately from one another so that the inheritance of one trait is not dependent on the inheritance of another.
Law of separation – Each inherited trait is defined by a gene pair. Parental genes are randomly separated to the sex cells so that sex cells contain only one gene of the pair. Offspring therefore inherit one genetic allele from each parent when sex cells unite in fertilization.
Polygenic Inheritance:Polygenic inheritance occurs when one characteristic is controlled by two or more genes. Often the genes are large in quantity but small in effect. Examples of human polygenic inheritance are height, skin color, eye color and weight.
Autosomal Dominant ·
Huntington Disease – degenerative brain disorder which results in loss of both mental and physical abilities– adult onset generally ·
Marfan Syndrome – disorder of connective tissue affecting the heart, blood vessels, lungs, eyes, bones, and ligaments ·
Syndactyly – webbing between toes and fingers ·
Polycystic Kidney Disease – a disease which causes cysts to grow on a person’s kidneys (and liver); the third leading cause of kidney failure in the United States ·
Brachdactyly – short fingers ·
Myotonic Dystrophy – a disorder that causes muscle weakness and the inability of muscles to relax after use. · porphyria – a group of disorders caused by a deficiency of an enzyme in the pathway for making heme (a component of hemoglobin)– this causes a variety of symptoms: sensitivity to light, mental changes which border on insanity, itchy and blistering skin, dark colored urine, abdominal pain and cramping, and hairiness
· Achondroplasia – growth defect causing abnormal body proportions, the arms and legs are very short while the torso is normal in size. · chronic simple glaucoma – increased pressure inside the eyeball · hypercholesterolemia -excessive levels of cholesterol in the blood stream ·
Polydactyly – extra toes and fingers ·
Ehlers-Danlos Syndrome – connective tissue disorders characterized by articular hypermobility (the ability to flex joints beyond the “normal” range), skin hyperelasticity (the ability to stretch the skin away from the body), and fragile skin and tissues (easy bruising and easily ruptured skin and blood vessels). ·
Neurofibromatosis – trait characterized by cafe-au-lait (“coffee and milk” pigmented skin) spots and small tumor-like growths on or under the skin– deformation of bones and curvature of the spine can also be symptoms 21 ·
nonsyndromic deafness – hearing loss due to a defective gene. Most defects affect the structure of the inner ear ·
Congenital cataracts – clouding of the lens in the eye ·
Familial high cholesterol – high cholesterol levels
Autosomal Recessive
· Tay-Sachs Disease – a degenerative disorder causing death usually by age 5 – Jewish heritage
· sickle cell anemia – disease causing the red blood cells in the body to have a sickle shape (not a round shape). These sickle shapes can block veins, arteries, and capillaries and cause blood flow to an area to be stopped for a while. This can have serious side effects such as tissue death and stroke.
· Beta-thalassenia (Cooley’s Anemia)- a defect in the beta chain of hemoglobin resulting in severe anemia
· galactosemia – individuals lack the enzyme that helps the body break down galactose.
· albinism (Oculocutaneous) – disorder characterized by absence of pigment in hair, skin, and eyes ·
agammaglobulinemia – defect that causes the ablesne of the white blood cells (B cells) causing recurrent bacterial infections · phenylketonuria – individuals with PKU cannot digest the amino acid phenylalanine (part of many proteins)– levels of phenylalanine rise in the bloodstream and cause brain damage ·
cystic fibrosis – A disease caused by defective chloride transport that leads to high levels of mucus in the lungs and pancreas, high sweat chloride levels, and other digestive and respiratory problems.
Sex-linked
X-Dominant
· ichthyosis simplex (d) Ichthyosis is a form of severe dry skin that causes affected areas to look like fish scales ·
Hypertrichosis – generalized hairiness covering the whole body
X-Linked -Recessive
hemophilia (r) – There is a defect in blood coagulation factor VIII which prevents blood clotting. This causes hemorrhage, easy bruising, and prolonged bleeding from wounds. ·
red-green colorblindness (r) – unable to distinguish between red and green ·
Duchenne’s muscular dystrophy (r) – a disease that begins to affect individuals between the ages 2 and 6. It causes muscle wasting and weakness. This can eventually affect all muscles of the body. Generally by age 10-12 affected individuals become confined to a wheelchair. ·
Anhidrotic Ectodermal Dysplasia – a group of disorders characterized by the absence of sweat glands, abnormal teeth, and hypotrichosis (less hair than normal) ·
Fragile X Syndrome – A disorder that causes various levels of mental impairment– from learning disabilities to severe retardation, both combined with delayed speech and language development. caused by more than 200 repeats of the trinucleotide CGG. Karyotypes of individuals with Fragile X Syndrome appear to be missing a small piece of the X chromosome near the end. ·
Lesch-Nyhan Disease – the absence of an enzyme HPRT (hypoxanthine-guanine phosphoribosyltransferase) causes an accumulation of uric acid in the urine and self-mutilative behavior 22
Y-linked ·
Hairy ears – hair grows on the pinnae of the ears– in some cases it is quite thick; in others it is only one · or two long hairs
Nondisjunction Autosomes:
· Down’s syndrome (trisomy 21) – an extra copy of the 21st chromosome– generally through · non-disjunction but occasionally the extra copy of critical chromosome material can be as · a result of translocation causing a combination of birth defects including some mental retardation · and characteristic facial features ·
monosomy 21 – a chromosome missing in pair 21.
Sex Chromosomes
· monosomy X (Turner’s syndrome)
· trisomy X · XXY (Klinefelter’s syndrome) · XYY · XXXX or XXXY
Multifactorial Inheritance (many genes + environment) ·
cleft palate and/or lip · club foot · congenital dislocation of the hip ·
spina bifida (open spine) · hydrocephalus (with spina bifida) · pyloric stenosis · diabetes mellitus – Type I diabetes – Individuals