autosomes non-sex chromosomes, homologous sex chromosomes one pair of the 23, two homologous in females and nonhomologous in males giemsa stain uses banding techniques, unambiguously numbered chromosomes, and individual variation in ch. composition can be studied, and missing or dulication portions often resulting in disease can be identified karyotype ordered display of chromosomes arranged according to size with homologous chromosomes paired together locus area of a chromosome occupied by a gene alleles different forms of a nucleotide sequence polymorphic a locus that has two or more alleles that occur with an appreciable frequency in a population genotype the composition of genes at a given locus phenotype outward appearance of an individual which is the result of both genotype and environment heterozygote effects of one allele mask those of another, dissimilar alleles at corresponding chromosome loci homozygous identical alleles at corresponding chromosome loci dominant allele whose effects are observable recessive allele whose effects are hidden codominance heterozygote is distinguishable from both homozygotes mode of inheritance pattern in which genetic disease is inherited through the generations of a family principle of segregation homologous genes separate from one another during reproduction and that each each reoproductive cell carries only one of the homologous genes prinicple of independent assortment hereditary transmission of one gene has no effect on the transmission of another chromosomal theory of inheritance behavior of chrmomosomes doews essentially correspond to Mendel's laws pedigree tool in analysis of modes of inheritance proband the beginning individual of the pedigree recurrence risk probability that subsequent children also will have the disease occurence risk probability that a child will have the disease consanguinity mating of two related individuals and the offspring are said to be inbred sex-linked trait conditions caused by genes located on the sex chromosomes sex-influenced trait occurs much more often in one sex than in the other crossing over new combinations of alleles can be formed recombination process of forming such new arrangements of alleles base pair substitution one base pair is replaced by another but is subtle and is not observable as chromosome abberations silent substitution amino acid change that does not occur frameshift mutation insertion of deletion of one or more base pairs to the CNA molecule, alters the resulting amino acid sequence mutagens large number of agents known to increase the frequency of mutations spontaneous mutation mutation that occurs in the absence of exposure to known mutagens mutational hot spots certain areas of some chromosomes that have particularly high mutation rates spontaneous abortions 50% of all recovered in 1st trimester have major chromosomal abberations amniocentesis detection method 16 wks fetal fibroblasts cultured for 2-3 wks and karyotyped risk of loss 0.5% only for at risk mothers and fetuses chorionic villus sampling 10 wk more cells collected and immediately sampled risk 1% euploid multiple of the normal number of chromosomes polyploid more than the diploid number of ch some normal (liver, bronchial and epithelial) have polyploidy triploidy three copies of each chromosome early in development and always lethal aneuploidy somatic cell that does not contain a multiple of 23 trisomy three copied of one chromosome may be survivable down's syndrome monosomy only one copy of a given ch lethal if autosome lethal if no x in male one x in female = turner's nondisjunction error in which homologous ch or sister ch fail to separate normally during meiosis or mitosis causes monosomy/trisomy partial trisomy only an extra portion of a chromosome is present in each cell less severe ch mosaics body has two or more different cell lines, each of which has a different karyotype, nondisjunction in 1 line of cells but not the other nondisjunction can happen when meiosis 1 or 2 trisomoy X females having three X ch in each cell sterility, menstrual irregularity, mental more X's = more severe klinefelters syndrome 47, XXY male appearance sterile half develop female breasts small testes sparse body hair and high voice tall metal retardation turners syndrome 45,X sterile females gonadal streaks instead of ovaries short and webbing of neck wide nipples carctation of aorta edema of feet reduced carrying angle at the elbow sparse body hair cri du chat deletion low birth weight mental ret microcephaly heart defects facial appearance and cat cry duplication less serious than deletion same region of deletion causes mental ret but normal physical characterisitics inversion balanced, no gain or loss of material inverted order after breaking no apparent physical effect position effect - change in gene's expression cause by its position translocation interchanging of genetic material between nonhomologous chromosomes lose no important genetic material carriers have no phenotypic differences but offspring will acute myelogenous leukemia robertsonian translocation fusion of 2 long arms carriers lose no important genetic material offspring have serious duplications/deletions reciprocal translocation breaks take place in two different chromosomes and material is exchanged carrier is normal offspring have problems fragile sites areas on chromosomes that develop distinctive breaks and gaps no apparent relationship to disease hot spot repeat of CGG fragile X syndrome fragile site on long arm of the X ch mental retardation S&S of fragile X machroordinism mental retardation large ears prominent jaw high pitched jocular speech Fragile X repeats normal 29 2X - man can carry 4X - man affected and can pass it on >700 - can see phenotype genetic anticipation worse in successive generations huntington's disease autosomal dominant, hereditary high penetrance neuronal aggregation of defective proteins no cure and few treatments affective more in spermatogenesis huntington's disease outcome number normal: 17-20 27-35: meiotically unstable 40-50: adult onset cases >50: juvenile onset demographics of Huntington's inherited through males 1/10000 western countries 5/500000 prevalence all ethnic groups onset 30-50 yo huntington's patho too many copies of CAG in huntingtin gene in exon 1 gain-of-function, negative dominant huntington's repeat aggregation in caudate, putamen, and striatum problems with huntington's dystonia chorea akinesia S&S of huntington's fidgetiness, restlessness chorea muscle spasms tics dystonic posturing falling difficulty swallowing/producing speech akinesia cognitive S&S of huntington's altered organization slowed processing of information difficulty learning new things difficulty planning and prioritizing difficulty multi-tasking impairment of space perception difficulty organizing incoming and outgoing words executive functions planning, working memory, attention, problem solving, verbal reasoning, inhibition, mental flexibility, multi-tasking, initiation and monitoring of actions psychiatric S&S of huntington's depression apathy personality changes anxiety/irritability obsession with certain activities delirium/mania dementia denial treating neurochemical symptoms of huntingtons GABA dopamine antagonists (haloperidol, phenothiazines) spontaneous mutation cause of disease in a child with no family history of the disease achondroplasia autosomal dominant 7/8 spontateous - mutation of FGFR3 NOT FROM HORMONES penetrance percentage of individuals with a specific genotype who also exhibit the phenotype age-dependent penetrance example huntington's disease - does not show up until later in life 30-50 therefore, penetrance increases with age incomplete pentrance gene is present but normal phenotype obligate carrier person with affected parent and affected child expressitivity extent of variation in phenotype associated with a particular genotype penetrance can be complete but expressitivity will alter the severity of the phenotype mechanisms altering expressitivity influenced by other genes environmental factors type of mutation neurofibromatosis retinoblastoma gene cafe-au-lait or malignant neurofibromas, scoliosis, seizures, gliomas, meuromas, hypertension, learning disabilities X inactivation turns off one X men have 0 normally women have 1 normally occurs at embryonic 7-14 days can be mom or dad but once inactivated, stable prader-willi syndrome genetic imprinting deletion of ch 15 on fathers side angelman syndrome genetic imprinting deletion of ch 15 on mothers side S&S of PW short stature obesity hypogonadism S&S of angelman mental retardation seizures ataxic gait autosomal recessive need two copies to get the disease carries normal phenotype siblings will have but not parents 1/4 of 2 carrier parents will have X-linked or mostly (dominant or recessive) recessive hemophilia A and fragile X sex is determined by... SRY gene XX with SRY = male phenotype XY without SRY Female phenotype most common X-linked... DMD progressive muscle degeneration code for muscle protein and when mutated, doesn't work cause of death in DMD pts respiratory and cardiac failure male example trait of disease male pattern baldness female examplet trait of disease autosomal dominant breat cancer linkage analysis see how often recombinations of certain genes take place crossing over during meiosis depends on linkage in situ hybridization . Lab technique to identify certain DNA segments/genes in a large piece of DNA/chromosome