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DNA is composed of
- Deoxyribose: pentose sugar molecule
- Phosphate molecule
- Nitrogenous bases: pyrimidines: Cytosine and Thymine, Purines: Adenine and Guanine
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Pyrimidines
Cytosine thymine
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Purines
Adenine and Guanine
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Genes
- Composed of DNA
- biologic and basic unites of inheritance
- Portions of chromosome with particular nucleotide sequence: code for proteins
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Chromosomes
- Composed by genes making up the genetic material in the nucleus
- Functions in transmission of genetic information
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# of chromosomes
- 23 chromosome pairs, 22 homologous pairs of autosomes, 1 pair sex linked
- 46 chromosomes
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Genotype
- the genetic constitution of an organism
- XX: female (homologous)
- XY: male (nonhomologous)
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Phenotype
any observable characteristic or trait of an organism
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Mitosis
- Preproduction and division of somatic (body) cells
- Chromosomes replicate
- 46 replicated chromosomes line up on spindle and one verson of each pulled into daughter cells
- each new cell contains the entire genetic information in 23 pairs of chromosomes
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Meiosis
- Reproductin of gametes (sperm and egg cells)
- Occurs in the reproductive cells (germ cells) of the ovary or testicle
- Involves two cell divisions resultion in four haploid cells with one of each chromosome paire
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DNA replication
- copy DNA
- weak hydrogen bonds are broken "unzipping" the DNA double helix
- Each chain serves as a template where teh complementary molecules attach and build the new double strand
- DNA is formed and replicated in the nucleus
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Protein Synthesis
- Occurs in cytoplasm, specifically in ribosomes
- DNA code is transported from nucleus into the cytoplasm
- Protein is then formed via transcription and translation
- Process is mediated by RNA
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RNA
- Ribonucleic Acid
- Similar to DNA except
- Sugar molecule (deoxyribose vs ribose)
- Uracil rather that Thymine as a base
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Transcription
messenger RNA (mRNA) is created and moves from nucleus into cytoplasm
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Translation
Complementary base pairing occurs with mRNA, which specifies the sequence of amino acids via transfer RNA (tRNA); ultimately results in the formation of a polypeptide chain
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mitosis unwanted changes
Genetic errors can change information of the daugter cells through: errors in replication, translocations, deletions, inversion, duplications, and more
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Meiosis unwanted changes
Errors result in germ cells with a potential for genetic diseases: Translocation, deletions, inversions, duplications, and sorting errors such as nondisjuction (failur to seperate)
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Mutation
- any inherited alteration of genetic material
- May cause disease or be subtle, silent substitutions, that do not change the amino acids
- rare events: rate of spontaneous mutation is 1/10,000 to 1/10,000,000
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base pair substitution
one base pair replaces another
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Frameshift mutation
insertion of deletion of one or more base pairs of the DNA molecule
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Mendelian disorders
- Single gene disorders
- Changes in single gene often a sigle codon which results in functional changes in the protein for which it codes
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Codon
a sequence of 3 bases in a strand
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Multifactoral or multigenic genetic disorders
- traits produced by multiple genes
- changes in many genes that contribute to a disease
- not considered officially as a strictly genetic disease, as environmental influences affect the expression of the trait
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Abberation
- Deviation from normal
- chromosomal aberrations are the leading known cause of mental retardation and miscarriage
- change in # of chromosomes
- change in shape of chromosomes
- addition of genetic information to a chromosome
- deletion of genetic information from a chromosome
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aneuploidy
- an abnormal # of chromosomes (change from 23 pairs)
- usually the result of nondisjunction
- to many is better than too few; loss of chromosome material is fatal
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Nondisjunction
- A failure to separate normally during meiosis or mitosis
- occurs in a variety of ways but the result is the same > an abnormal number of chromosomes in the daughter cells
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aneuploidy due to nondisjunction in meiosis
upon fertilization the resulting cell has either 1 or 3+ copies of the chromosome rather than the standard pair
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Aneuploidy due to nondisjunction in mitosis
results in cells with less than or more than the full complement of chromosmes (often seen in cancer cells)
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Autosomal aneupoidy: trisomy 21
- Down Syndrome: Extra copy of chromosome 21
- 1/800 to 1/1000 births (risk increases with maternal age)
- Face: low nasal bridge, epicanthal folds, protruding tongue, low-set ears
- MSK: hypotonia, short stature
- Systemic disorders: congenital heart disease, reduced ability to fight resp infections, intestinal stenosis, increase susceptibility to leukemia
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hypotonia
poor muscle tone
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other autosomal aneuploidys
- trisomy 13 or 18: rare occurence, sever retardation, survive a few weeks- a year
- trisomy 8,9, or 22: exist rarely
- except for sex chromosomes and chromosome 21, monosomy and trisomy are probably not compatible with life
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Sex chromosome aneuploidy
Many varieties of intersex conditions, now called disorders of sex development
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Klinefelter syndrome
- Disorder of sex development
- 47 chromosomes (2+ X's Ex:XXY)
- 1/1000 male births (often not diagnosed until puberty)
- male appearance but usually sterile
- abnoral sexual development and feminization: testicular atrophy, infertility, tall, long arms and legs, feminine hair distribution, gynecomastia, high pitched voice, impaired intelligence
- treatment: testosterone
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Turner Syndrome
- Disorder of sex development
- 45 chromosomes (monosomy X)
- 1/5000 female births with high pre/postnatal mortality (increased with paternal age/damaged x)
- Female phenotype: short stature, webbing of neck, sterility, fibrous ovaries, amenorrhea, wide chest, congenital heart defects
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Deletions
Broken chromosomes and lost DNA (cri du chat short arm of chromosome 5 missing)
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Duplications
addition of genetic material (duplication of chromosome 5 mental retardation but less serious physical defects that deletion)
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translocation
interchange of genetic material between non-homologous chromosomes
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inversion:
When two breaks take place on a chromosome and an inverted reinsertion of the missing fragment takes place
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Cri du Chat Syndrome
- Deletion short arm chromosome 5
- severe retardation, round face, congenital heart anomalies
- infant crying resembles a cat
- some live to adulthood
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Autosome
any chromosome other than the sex chromosome
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autosomal dominant trait
- males and female children are equally affected
- only need one affected parent
- if you have gene you have disease (severity (expression) varies)
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Marfan syndrome
- Autosomal dominant
- a genetic disorder of the connective tissues due to a mutation of a protein
- mutation of fibrillin 1 gene on chromosome 15
- characterized by long thin extremeties, reduced vision due to dislocation of the lens, cardiovascular abnormalities (mitral valve prolapse, and aortic dissections), chest deformities
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fibrillin 1, marfan fibrillin 1
- Fibrillin 1: a glycoprotein secreted by fibroblasts provides inmortant scaffolding for deposition of other matrix proteins such as elastin
- Marfan Fibrillin 1: more susceptible to proteolytic degradation than normal fibrillin, leading to weak connective tissues
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Autosomal Recessive Trait
- Males and females equally affected
- Parent may but probably dont have (are carriers)
- expression variable
- cystic fibrosis, alpha 1 antitrypsin deficiency, phenylketonuria, sickle cell anemia, albinism
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albinism
- autosomal recessive
- lack pigmentation: hair skin eyes
- at least 6 different forms of oculocutaneous albinism
- some are associated with organ defects
- lack enzyme tyrosinase which catalyzes the formation of dopa from tyrosine. Dopa is the precursor of melanin
- Risk for sunburn skin cancer impaired vision and photo sensitivity
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Cystic Fibrosis
- Autosomal recessive
- 70% from one mutation but > 800 mutations identified
- characterized by: thick tenacious secretions in lung, gi, gu, resp tract infections, meconium ileus, pancreatic failure, infertility
- now can survive to middle age, commonly with lung transplant
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Sex-linked disorders
- disorders caused by genes located on sex chromosomes
- X-linked recesssive diseases much more common
- more males affected, women are generally carriers
- hemophilia A (factor VIII deficiency)
- Duchenne muscular dystrophy
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Hemophilia A
- Sex-linked disorders
- factor VIII deficiency
- Queen victoria was 1st carrier in bristish royal line
- about 15-20% of genetic defects aris from spontaneous mutation (cant blame mom)
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Duchenne Muscular dystrophy
- Lack dystrophin (protein that provides the structural integrity for muscle membranes)
- Results in severe muscle wasting
- usually survive to mid-twenties
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Multifactorial (polygenic) diseases
- traits produced by several genes acting together
- not considered a genetic condition in the sense of being produced by a single gene
- environmental factors influence the expression of the train (height iq)
- asthma, schizophrenia, adult onset diabetes, hypertension
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Environmentally induced congenital disorders (teratogens)
- any agent that can disrupt the develpment of the embryo or fetus: cause errors by interfering with cell proliferation, migration, or differentiation
- Congenital disorders can arise if development is affected
- Nutritional: folic acid
- Chemicals/drugs: cocaine, fetal ETOH, tetracyclines
- Infections: viral (chickenpox)
- Radiation:
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Environmentally induced congenital disorders (susceptibility to teratogens)
- Amount of exposure
- fetal age when exposed
- any prior conditions of the mother
- genetic predisposition of the fetus
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prenatal tests
- ultrasounds
- pedigree analysis: mapping determine chromosomal location of genes
- Embryoscopy: allows direct visualization of the embryo as early as the first trimester
- Chorionic Vilus Sampling: usually 10-12 weeks, the genetic material in chorionic villus cells is the same as that in the babys cells
- amniocentisis: week 15-20 a test to study amniotic fluid looking for sex of baby, chromosome problems, lung maturity, infection
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Fetal alcohol syndrome
- associated with low socioeconomic status
- growth retardation, neurologic disorder, malformations of head and face (epicantal folds, flat nasal bridge, small peripheral fissure, railroad track ears, upturned nose, smooth phyltrum, thin upper lip), atrial septal defects
- mechanisms include maternal fetal hypoxia and excessive free radical production
- alcohol causes acute and transient collapse of the umbilical cord which could damage the fetus by interrupting its oxygen supply
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TORCH
- Toxoplasmosis, others (hep B, coxsackievirus B, mumps, poliovirus), rubella, Cytomegalovirus, herpes
- microorganisms cross the placenta and infect the developing fetus
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Rubella
- Risk of infection begins just prior to conception and extends to 20 weeks gestation after which the virus rarely crosses the placenta
- cataracts, deafness, and heart defects
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Toxoplasmosis
- contracted from ingestion of raw or undercooked meat and more rarely from contact with cat feces
- risk of congenital toxoplasmosis is somewhat lower if infection occurs during the first trimester than in if in the third.
- Hypatosplenomegaly, thrombocytopenia, microcephaly, convulsions, fever, and small for gestational age; hydrocephalus; chorioretinitis (rare), feeding difficulties, small areas of hemorrage (petechiae, purpura), jaundice, hearing impairment, small eyes
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periods of fetal vulnerability
- prior to 1 week: teratogens generally either damage so few cells that embryo develops normally or so many cells that spontaneous abortion occurs
- 3-9 weeks: embryo is very vulnerable to teratogens. 4-5 weeks is peak of susceptibility
- 3-9 months: susceptibility to error of morphogenisis is sig less, fetal insults after the third month are more likely to result in growth retardation or injury to normally formed organs
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