Genetics

• Deoxyribose: pentose sugar molecule
• Phosphate molecule
• Nitrogenous bases: pyrimidines: Cytosine and Thymine, Purines: Adenine and Guanine

Cytosine thymine

Adenine and Guanine

• Composed of DNA
• biologic and basic unites of inheritance
• Portions of chromosome with particular nucleotide sequence: code for proteins

• Composed by genes making up the genetic material in the nucleus
• Functions in transmission of genetic information

• 23 chromosome pairs, 22 homologous pairs of autosomes, 1 pair sex linked
• 46 chromosomes

• the genetic constitution of an organism
• XX: female (homologous)
• XY: male (nonhomologous)

any observable characteristic or trait of an organism

• 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

• 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

• 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

• 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

• Ribonucleic Acid
• Similar to DNA except
• Sugar molecule (deoxyribose vs ribose)
• Uracil rather that Thymine as a base

messenger RNA (mRNA) is created and moves from nucleus into cytoplasm

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

Genetic errors can change information of the daugter cells through: errors in replication, translocations, deletions, inversion, duplications, and more

Errors result in germ cells with a potential for genetic diseases: Translocation, deletions, inversions, duplications, and sorting errors such as nondisjuction (failur to seperate)

• 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

one base pair replaces another

insertion of deletion of one or more base pairs of the DNA molecule

• Single gene disorders
• Changes in single gene often a sigle codon which results in functional changes in the protein for which it codes

a sequence of 3 bases in a strand

• 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

• 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

• 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

• 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

upon fertilization the resulting cell has either 1 or 3+ copies of the chromosome rather than the standard pair

results in cells with less than or more than the full complement of chromosmes (often seen in cancer cells)

• 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

poor muscle tone

• 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

Many varieties of intersex conditions, now called disorders of sex development

• 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

• 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

Broken chromosomes and lost DNA (cri du chat short arm of chromosome 5 missing)

addition of genetic material (duplication of chromosome 5 mental retardation but less serious physical defects that deletion)

interchange of genetic material between non-homologous chromosomes

When two breaks take place on a chromosome and an inverted reinsertion of the missing fragment takes place

• Deletion short arm chromosome 5
• severe retardation, round face, congenital heart anomalies
• infant crying resembles a cat
• some live to adulthood

any chromosome other than the sex chromosome

• males and female children are equally affected
• only need one affected parent
• if you have gene you have disease (severity (expression) varies)

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• Lack dystrophin (protein that provides the structural integrity for muscle membranes)
• Results in severe muscle wasting
• usually survive to mid-twenties

• 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

• 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:

• Amount of exposure
• fetal age when exposed
• any prior conditions of the mother
• genetic predisposition of the fetus

• 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

• 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

• Toxoplasmosis, others (hep B, coxsackievirus B, mumps, poliovirus), rubella, Cytomegalovirus, herpes
• microorganisms cross the placenta and infect the developing fetus

• 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

• 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

• 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