Deoxyribonucleic Acid (DNA) DNA structure

A, Double helix. Shown with the phosphodiester backbone as a ribbon on top and a space-filling model on the bottom. The bases protrude into the interior of the helix where they hold it together by base pairing. The backbone forms two grooves, the larger major groove and the smaller minor groove. B, Base pairing holds strands together. The hydrogen (H)-bonds that form between A and T and between G and C are shown with dashed lines. These produce AT and GC base pairs that hold the two strands together. This always pairs a purine with a pyrimidine, keeping the diameter of the double helix constant. A, Adenine; C, cytosine; G, guanine; T, thymine. (From Raven PH et al: Biology, ed 8, New York, 2008, McGraw-Hill.) 3
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V1 (2:12) V2 ( 5: 23) 4
DNA (cont’d) Chromosomes contain genes. Genes are the basic unit of inheritance and are composed of DNA. DNA subunit or nucleotide contains: One pentose sugar (deoxyribose) One phosphate group One nitrogenous base Cytosine (C), thymine (T), adenine (A), guanine (G) DNA has a double helix structure.
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DNA as the Genetic Code DNA provides the code for all body proteins. Proteins are composed of one or more polypeptides. Polypeptides are composed of amino acids; there are twenty (20) amino acids: The sequence of three bases (codons) direct the production of amino acids. Termination and nonsense codons stop the production of protein.
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Replication The DNA strand is untwisted and unzipped. Single strand acts as a template. DNA polymerase pairs the complementary bases. Adenine-thymine; cytosine-guanine DNA polymerase adds new nucleotides and “proofs” the new protein; if not correct, the incorrect nucleotide is excised and replaced.
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-The DNA bases code for amino acids which in turn make up proteins. The amino acids are specified by triplet codons od nitrogenous bases -Transcription and translation are 2 processes in which proteins are specified by DNA and involves RNA. RNA is chemically similar to DNA except it is single stranded and has Uracil instead of Thymine as one of its 4 bases. -Meiosis is process by which haploid cells are made from diploid cells 7
Replication (cont’d) Replication process
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Replication (cont’d) Question 1 Which information is correct regarding DNA polymerase? DNA polymerase functions to: Signal the end of a gene. Pull apart a portion of a DNA strand. Add the correct nucleotides to a DNA strand. Provide a template for the sequence of mRNA nucleotides.
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Mutation Is any inherited alteration of genetic material. Chromosome aberrations in number or structure Base pair substitution or missense mutation One base pair is substituted for another; may result in changes in amino acid sequence. May or may not cause disease or problems. Frameshift mutation Involves the insertion or deletion of one or more base pairs to the DNA molecule. Mutagens: Are agents, such as radiation and chemicals, that increase the frequency of mutations.
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From Genes to Proteins DNA is formed in the nucleus; protein is formed in the cytoplasm. Transcription and translation: DNA code is transported from the nucleus to the cytoplasm, and protein is subsequently formed. Ribonucleic acid (RNA) mediates both processes. RNA is a single strand. Uracil rather than thymine is one of the four bases; all the rest are the same as DNA.
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Transcription RNA is synthesized from the DNA template via RNA polymerase. RNA polymerase binds to the promoter site on DNA. DNA specifies a sequence of mRNA. Transcription continues until the termination sequence is reached. mRNA then moves out of the nucleus and into the cytoplasm. Gene splicing occurs. Introns and extrons
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Transcription (cont’d)
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General Scheme of RNA Transcription. In transcription of messenger RNA (mRNA), a DNA molecule “unzips” in the region of the gene to be transcribed. RNA nucleotides already present in the nucleus temporarily attach themselves to exposed DNA bases along one strand of the unzipped DNA molecule according to the principle of complementary pairing. As the RNA nucleotides attach to the exposed DNA, they bind to each other and form a chainlike RNA strand called a messenger RNA (mRNA) molecule. Notice that the new mRNA strand is an exact copy of the base sequence on the opposite side of the DNA molecule. As in all metabolic processes, the formation of mRNA is controlled by an enzyme—in this case, the enzyme is called RNA polymerase. (From Ignatavicius DD, Workman LD: Medical-surgical nursing, ed 6, St Louis, 2010, Saunders.) 13
Translation Is the process by which RNA directs the synthesis of a polypeptide via the interaction with transfer RNA (tRNA). tRNA contains a sequence of nucleotides (anticodon) complementary to the triad of nucleotides on the mRNA strand (codon). Ribosome is the site of protein synthesis. Ribosome helps mRNA and tRNA make polypeptides. When ribosome arrives at a termination signal on the mRNA sequence, translation and polypeptide formation cease.
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Ribosomes are key 14
Translation (cont’d) Question 2 At what site does protein synthesis occur? The site of protein synthesis is the: Codon Intron Ribosome Anticodon
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Chromosomes Somatic cells Contain 46 chromosomes (23 pairs) One member from the mother; one from the father Diploid cells Gametes Sperm and egg cells Contain 23 chromosomes Haploid cells One member of each chromosome pair Meiosis Formation of haploid cells from diploid cells
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-Human cells consist of diploid somatic cells (body cells) and haploid gametes (sperm and egg cells) 16
Chromosomes (cont’d) Autosomes Are the first 22 of the 23 pairs of chromosomes in males and females. The two members are virtually identical and are thus said to be homologous. Sex chromosomes Make up the remaining pair of chromosomes. In females, it is a homologous pair (XX). In males, it is a nonhomologous pair (XY). Karyotype The length and centromere location determine the ordered display of chromosomes.
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-Humans have 23 pairs of chromosomes ; 22 of the 23 pairs are autosomes ( are homologous/the same) in both males and females. The remaining pair consists of sex chromosomes. -Females have 2 homologous X chromosomes as the sex chromosomes. Males have an X and Y nonhomogolous chromosome. 17
Chromosomal Aberrations Euploid cells Have a multiple of the normal number of chromosomes. Haploid and diploid cells are euploid forms. Polyploid cells: An euploid cell has more than the diploid number. Triploidy: Is a zygote that has three copies of each chromosome. Tetraploidy: Has four copies of each chromosome (92 total). Triploid and tetraploid fetuses do not survive or are stillborn or spontaneously aborted.
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Chromosomal Aberrations (cont’d) Aneuploidy Is a somatic cell that does not contain a multiple of 23 chromosomes. Trisomy (trisomic): Is a cell that contains three copies of one chromosome. Infants can survive with trisomy of certain chromosomes. Monosomy Is the presence of only one copy of any chromosome. Is often fatal.
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-Aneuploid cells contain 3 copies of one chromosome is known as trisomy -Monosomy is the presence of only one copy of a chromosome in a diploid cell -Abnormalities of chromosomal structure include deletions, duplications, inversions, and translocations. 19
Chromosomal Aberrations (cont’d) Aneuploidy of sex chromosomes Usually presents less serious consequences than autosomes. Y chromosome usually causes no problems since it contains little genetic material. For the X chromosome, inactivation of extra chromosomes largely diminishes their effect.
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Chromosomal Aberrations (cont’d) Nondisjunction Is usually the cause of aneuploidy. Is the failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis.
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-Difficulty in separation of chromosomes 21
Chromosomal Aberrations (cont’d) Nondisjunction (cont’d)
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Nondisjunction Causes Aneuploidy When Chromosomes or Sister Chromatids Fail to Divide Properly. (From Jorde LB et al: Medical genetics, ed 5, Philadelphia, 2016, Elsevier.) 22
Autosomal Aneuploidy Trisomy Chromosomes 13, 18, and 21 can survive; most others do not. Partial trisomy Only an extra portion of a chromosome is present in each cell. Is not as severe as trisomies. Chromosomal mosaics Are trisomies that occur in only some cells of the body. Body has two or more different cell lines, each of which has a different karyotype.
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Autosomal Aneuploidy (cont’d) Down syndrome Is the best-known example of aneuploidy. Trisomy 21 Occurs 1 in 800 live births. Manifestations: Mental challenges; low nasal bridge; epicanthal folds; protruding tongue; flat, low-set ears; and poor muscle tone. Risk increases with maternal age. Has an increased risk of congenital heart disease, respiratory infections, and leukemia.
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Autosomal Aneuploidy (cont’d) Down syndrome (cont’d)
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 Down Syndrome. A, The karyotype of Down syndrome consists of 47 chromosomes and shows trisomy 21. B, A child with Down syndrome. (From Damjanov I: Pathology for the health professions, ed 4, Philadelphia, 2012, Saunders.) 25
Sex Chromosome Aneuploidy Occurs 1 in 400 males and 1 in 650 females. Trisomy X is one of the most common aneuploidy. Females have three X chromosomes. Occurs 1 in 1000 female births. Symptoms are variable and include sterility, menstrual irregularity, and/or cognitive deficits. Symptoms worsen with each additional X chromosome.
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-Mental function is more severely impaired with greater number of trisomy in X chromosomes, for example some patients have 4-5 X chromosomes instead of just 3. 26
Sex Chromosome Aneuploidy (cont’d) Turner syndrome Females have only one X chromosome Denoted as karyotype 45,X. Characteristics include: Absence of ovaries (sterile) Short stature Webbing of the neck Widely spaced nipples High number of aborted fetuses X chromosome that is usually inherited from the mother Occurs 1 in 2500 female births. Teenagers receive estrogen.
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-Most teenagers treated with estrogen to promote development of secondary sexual characteristics. Dose is then reduced to maintain characteristics and help avoid osteoporosis. Human growth hormone sometimes given to increase stature. 27
Sex Chromosome Aneuploidy (cont’d) Turner syndrome (cont’d)
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Turner Syndrome. A sex chromosome is missing, and the person's chromosomes are 45,X. Characteristic signs are short stature, female genitalia abnormality, webbed neck, shieldlike chest with underdeveloped breasts and widely spaced nipples, and imperfectly developed ovaries. (From Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.) 28
Sex Chromosome Aneuploidy (cont’d) Klinefelter syndrome Individuals with at least one Y and two X chromosomes. Characteristics include: Male appearance Femalelike breasts (gynecomastia) Small testes Sparse body hair 1 in 1000 male births Some individuals can be XXXY and XXXXY; will have male appearance; abnormalities will increase with each X; can also have an extra Y chromosome. Disorder increases with the mother’s age.
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-Stature is often elevated along with moderate degree of mental impairment. 29
Sex Chromosome Aneuploidy (cont’d) Klinefelter syndrome (cont’d)
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Klinefelter Syndrome. This young man exhibits many characteristics of Klinefelter syndrome: small testes, some development of the breasts, sparse body hair, and long limbs. This syndrome results from the presence of two or more X chromosomes with one Y chromosome (genotypes XXY or XXXY, for example). (Courtesy Nancy S. Wexler, PhD, Columbia University. Picked up from Patton KT, Thibodeau GA: Anatomy & physiology, ed 9, St Louis, 2016, Mosby.) 30
Sex Chromosome Aneuploidy (cont’d) Question 3 A female has one X chromosome. Which diagnosis will the nurse observe documented on the chart? Trisomy X syndrome Klinefelter syndrome Fragile X syndrome Turner syndrome
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Abnormalities of Chromosomal Structure Effects may or may not have serious consequences. Chromosome breakage If a chromosome break occurs, then the break is usually repaired with no damage. Breaks can stay or can heal in a way that alters the structure of the chromosome. Can occur spontaneously. Agents of chromosome breakage include Ionizing radiation, chemicals, and viruses.
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Abnormalities of Chromosomal Structure (cont’d) Deletions Chromosome breakage or loss of DNA Example: Cri du chat syndrome or “cry of the cat” Low birth weight, mentally challenged, and microcephaly Duplications Excess genetic material Usually have less serious consequences Inversion Chromosomal rearrangement in which a chromosome segment is inverted: ABCDEFG becomes ABEDCFG Usually affects offspring
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Abnormalities of Chromosomal Structure (cont’d) Infant with cri du chat (5p deletion) syndrome
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-Occurs as a result of deletion of part of short arm portion of chromosome 5. Although one copy of chromosome is normal, serious consequences can still occur with deletions. -Name derived from distinctive cry of newborn with this condition, -Other symptoms include severe mental retardation, microcephaly, heart defects, and typical facial appearance seen in figure above. 34
Abnormalities of Chromosomal Structure (cont’d) Fragile sites (cont’d) Fragile X syndrome Site is on the long arm of the X chromosome; has an elevated number of repeated DNA sequences. Is associated with being mentally challenged; is second in occurrence to Down syndrome.
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-Caused by an elevated number of repeated DNA sequences (more than 200) in the first exon of the fragile X gene. DNA replication becomes unstable, more than 20 genetic diseases are linked to this mechanism. 35
Elements of Formal Genetics Genetic inheritance Mechanisms by which an individual’s set of paired chromosomes produces traits. Explains the patterns of inheritance for traits and diseases that appear in families. Mendelian traits Are inherited traits primarily attributed to single genes.
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Elements of Formal Genetics (cont’d) Locus: Is the location occupied by a gene on a chromosome. Allele: Is one of several different forms of a gene at a locus. One member of a gene from the mother; one member of a gene from the father Homozygous: When genes are identical Heterozygous: When genes are different Polymorphism or polymorphic Is a locus that has two or more alleles that occur with appreciable frequency.
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37 37 The way chromosomes are paired can produce specific traits.
Elements of Formal Genetics (cont’d) Genotype: Is the composition of genes at a given locus. Phenotype Is the outward appearance of an individual. Results from genotype and the environment. Example: Infant with phenylketonuria (PKU) has the PKU genotype. If left untreated, the infant will have cognitive impairments, which is the PKU phenotype. If treated, the infant will still have the PKU genotype but can have a normal phenotype.
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-An individual’s genotype is his or her genetic makeup, and the phenotype reflects the interaction of the genotype and environment 38
Elements of Formal Genetics (cont’d) Dominance and recessiveness If two alleles are found together, then the allele that is observable is dominant and the one whose effects are hidden is recessive. In genetics, the dominant allele = a capital letter, and the recessive allele = a lowercase letter. Alleles are either heterozygote or homozygote. Alleles can be co-dominant; that is, both alleles are expressed. Carrier Has a disease allele but is phenotypically normal. Can pass disease to offspring.
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-At a heterozygous locus, a dominant gene’s effects mask those of a recessive gene. The recessive gene is expressed only when it is present in 2 copies. 39
Transmission of Genetic Diseases Mode of inheritance: Is the inherited patterns through the generations of a family. Mendel’s two laws Principle of segregation Homologous genes separate from one another. Each cell carries only one of the homologous genes. Principle of independent assortment Hereditary transmission of one gene has no effect on the transmission of another. Chromosome theory of inheritance Chromosomes follow Mendel’s two laws.
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Transmission of Genetic Diseases (cont’d) Four major types of genetic diseases Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive
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Genetic diseases caused by a single gene usually follows autosomal dominant, autosomal recessive, or X-linked recessive modes of inheritance 41
Transmission of Genetic Diseases (cont’d) Pedigree Is the tool used to study specific genetic disorders within families. Begins with the proband. Propositus (male) or proposita (female) Usually the first person in the family diagnosed or seen in a clinic
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-Pedigree charts are important tools in the analysis of modes of inheritance -Propositus/proposita is the individual who usually is the first diagnosed or seen in clinic with the disease 42
Autosomal Dominant Inheritance Diseases are rare. Occurs in fewer than 1 of 500 individuals. The union of a normal parent with an affected heterozygous parent usually produces the affected offspring. An affected parent can pass either a disease gene or a normal gene to his or her children; each event has a probability of 0.5; on average, half will be heterozygous and will express the disease and half will be normal.
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- No generational skipping occurs. -Condition is expressed equally in males and females, and males and females are equally likely to pass the gene to his or her offspring. -Recurrence risk: probability that family member will have genetic disease -When one parent is affected by an autosomal dominant disease and the other is normal, the occurrence and recurrence risks for each child are one half. -Each birth is an independent event. -New mutation: Is when no history of an autosomal dominant condition is present, but the child develops the mutation. -Offspring of affected child will have 50% chance of genetic disease (recurrence risk) 43
Autosomal Dominant Inheritance (cont’d) Characteristics of autosomal dominant inheritance Condition is expressed equally in males and females, and males and females are equally likely to pass the gene to his or her offspring. Approximately one-half of children of an affected heterozygous parent will express the condition (all or none of the children may have the condition). No generational skipping occurs.
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Autosomal Dominant Inheritance (cont’d) Recurrence risk (cont’d)
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Review figure 4-20 on page 153 Punnett Square and Autosomal Dominant Traits. A, Punnett square for the mating of two individuals with an autosomal dominant gene. Here both parents are affected by the trait. B, Punnett square for the mating of a normal individual with a carrier for an autosomal dominant gene.


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