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Principles of Inheritance GENETICS • • • • • DNA found in nucleus of each cell composes chromosomes chromosomes contain genes genes-biological blueprints dictate how we look, how our body functions & may be even how we behave • traits are inherited • passed down from generations before us • science of heredity-genetics Genetics • modern science of genetics-began 1860 • Gregor Mendel • Father of Genetics • helped lay down principles of modern genetics • Central European monk • conducted experiments using garden peas • ideas were published in 1860's • unrecognized until after his death • not appreciated until early 1900s • work applies to humans as well as peas • illustrates basic rules of inheritance Rules of Inheritance • Mendel discovered basic genetic principles breeding garden pea plant • exercised strict control over mating of these plants • studied seven characteristics • each with two possible forms Rules of Inheritance • most important conclusion: inherited variations are transmitted to offspring as discrete units • until this time most assumed characteristics of individual organisms were blended from generation to generation • particulate theory • Particles-now known as genes GENE True Breeding Plants • before beginning Mendel worked with his plants to ensure he had true-breeding plants • produce offspring that are identical to parents • purple flowers purple offspring Hybridization-CrossBreeding • purple mom + white dad • hybridization • or simply-cross • offspring are hybrids Cross-Breeding • true breeding parentsP generation –for parental • children-F1 generation –f=filial-Latin for son • when F1 plants are matedoffspring-F2 generation Mendel’s Experiments • Mendel noticed that traits were transmitted in predictable ways from parents to offspring • crossed different strains of purebred plants & studied their progeny • at first worked with consequences of crossing one trait at a time • monohybrid cross • would cross purple plant with white plant & look at color of offspring • F1 generation-always purple • Mendel wondered what had happened to heritable factor for white Mendel’s Experiments • when crossed F1 generations • missing white factor reappeared • 75% of offspring had purple flowers • 25% had white flowers • 3:1 ratio Mendel’s Experiments • same pattern of inheritance was found for all characteristics of pea plant • in cross-pollinating green pods-first offspring generation (f1) always had green pods • f2 generation consistently had 3:1 ratio of green to yellow Mendel’s Conclusions • white or yellow genes do not disappear in f1 generation • masked by purple or green gene • individuals inherit one unit from each parent for each trait • specific trait may not show up in an individual • may be passed to next generation • from his results, Mendel described four specific hypotheses Mendel’s Hypotheses • there are alternative forms of genes-alleles • for each inherited characteristic an organism must have 2 genes – one from each parent • maybe-same or different • two of same allelehomozygous • two different allelesheterozygous Mendel’s Hypotheses • alleles represent genotype • when alleles are differentallele that determines appearance (phenotype) is dominant • other allele has no observable effect on phenotype-recessive • dominant genes-always expressed • need only one dominant gene to have particular phenotype • to have recessive characteristicmust carry two recessive genes – unless gene is located on sex chromosome • customary to use capital letters for dominant traits • small letters for recessive ones Genotype & Phenotype • brown eye color is dominant (B) • blue (b) is recessive • person with genotype BB or Bb would have brown eyes • person with genotype bb would have blue ones Law of Segregation • each f1 generation plant inherits one allele from one parent & one allele from other • when f1 plants mated, each allele had equal chance of being passed on to offspring • for any particular trait, pair of alleles from each parent separate • only one allele passes from each parent to offspring • which allele in parent's pair is inherited is-chance Law of Segregation • genes occur in pairs because chromosomes occur in pairs • during gamete productionmembers of each gene pair separate so each gamete contains one member of a pair • during fertilization full number of chromosomes is restored • members of a gene or allele pair are reunited • segregation of alleles occurs during process of gamete formation-meiosis Punnett Square • used to illustrate basic rules of inheritance • shows alleles of mother and alleles of father • by simple multiplication one can figure out probability of obtaining offspring with characteristics of parents Punnett Square Examples Example • Brown eyed father-BB • Blue eyes-mother-bb • Recessive trait Example • father with red hair • recessive trait • has children with mother with black hair • dominant trait • probability of having children with red hair is • ? • each child would carry a gene for red hair • this is the case if mother has two dominant alleles in her genotype • what if we know that woman’s mother had red hair r R R Rr Rr r Rr Rr Dihybrid Cross • Mendel next crossed & followed inheritance of two traits at same time • dihybird crosses Dihydrid Crosses • two characteristics Mendel studied were seed shape & color • seeds were either green or yellow & either wrinkled or round • knew round & yellow were dominant • wrinkled & green were recessive • wondered what would happen in a dihybrid cross • mating GGWW pea with ggww one Principle of Independent Assortment • f1 generation yielded heterozygous hybrids or RrYy • phenotype was round & yellow • when f1 generation was crossed found distribution of one pair of alleles into gametes did not influence distribution of other pair • genes controlling different traits are inherited independently of one another • Principle of Independent Assortment • ratio was 9:3:3:1 • 9 yellow, round, 3 green, round, 3 yellow, wrinkled and one completely recessive pea or green, wrinkled Punnett Square Test Crosses • used to determine genotype of specific specimens • have a purple flowering pea plant • want to know if pea plant has purple flowers because it is homozygous or heterozygous • unknown plant is mated with known plant • cross purple-flowered unknown with white-flowered plant (completely recessive) • if all offspring exhibited purple flowersconclude unknown parent is homozygous • if offspring exhibited 1:1 ratio of purple to white flowersconclude unknown parent is heterozygous Mendelian Pattern Inheritance • • • • • • • • • • • genes coding for a particular trait are located at particular positions on chromosomes-loci come in several forms-alleles receive one allele from each parent if identical-homozygous for a trait if different-heterozygous recessive traits are not expressed in heterozygotes for recessive alleles to be expressed, one must have 2 copies dominant traits can be expressed in presence of another, different allele dominant alleles prevent expression or mask recessive alleles in heterozygotes. traits that are result of one set of genes are single gene traits transmission of single gene traits follows Mendel’s patterns of inheritance Other Patterns of Inheritance • over 4,500 human trains are inherited according to simple Mendelian principles • there are exceptions to Mendel’s rules Incomplete dominance • offspring is heterozygous for a trait but phenotype is intermediate between phenotypes of homozygous parents • heterozygous snapdragons of white & red parents have pink flowers • sickle cell disorder • homozygous individuals have either normal blood or sickle cell anemia • heterozygous individuals have sickle cell trait Incomplete Dominance Codominance • phenotypes for both alleles at a locus are expressed at same time • human ABO blood system shows both simple Mendelian inheritance & codominance • A & B alleles are dominant to O • if have genotype AOblood type is A • if BOblood type is B • however, neither A or B alleles are dominant to one another • codominant-both traits are expressed • person with allele for A & one for B has blood type AB • OO = Blood type O AO = Blood type A BO = Blood type B AB = Blood type AB AA = Blood type A BB = Blood type B Polygenetic Inheritance • characteristics due to multiple alleles • many genes define a trait • Height • combination of genes for height of face, size of vertebrate & length of leg bones • skin color-due to interactions between at least 3 pairs of alleles • continuous traits • show gradations • there is a series of measurable intermediate forms between 2 extremes Sex-Linked Genes • characteristics found on X & Y chromosome • inherited differently • X linked, recessive shows effect more in males • Recessive – no corresponding gene on Y chromosome – therefore trait will be expressed Chromosomes • every nucleus in every somatic or body cell carries genetic blueprint for who we are • 46 chromosomes • each paired with a like chromosome • 23 pairs • 23 chromosomes came from our mothers • 23 from our fathers Sex Chromosomes • exception found • • • • with sex chromosomes X& Y chromosomes other 22 pairs are autosomes sex chromosomes determine gender XX = girl & XY = boy Sex-Linked Traits • sex linkage – results from action of genes present on sex chromosomes • most located on X chromosome • nearly all are recessive • most X-linked genes have no homologous loci on Y chromosome • baldness, color blindness & hemophilia • occur more in males than females • males receive only one allele of a gene located on X chromosome • therefore even recessive alleles will be expressed in males • there is no dominant gene to mask it Inheritance of Sex-Linked Genes • • • • • • • • • • • for sex linked traits-females are carriers if have one recessive allele affected when possess 2 recessive alleles affected fathers pass X-linked allele to all daughters but not to sons males receive X chromosomes only from mothers mothers can pass sex-linked alleles to both sons & daughters unaffected males do not carry defective gene carrier female has 50% chance of producing affected son 50% chance of producing carrier daughter affected females are homozygous-rare condition requires both carrier mom and father with the condition Genetic Disorders • can be inherited as dominant or recessive traits by simple Mendelian principles • dominant disorders-inherited when one copy of dominant allele is present • recessive disorders require presence of two copies of recessive gene • disorders may be present at birth or become evident later in life • most inherited from parents • 15-20% are result of new mutations – molecular alterations in genetic material, arising during fetal development • disorders are classified according to location of defective gene-autosomal or sex & mode of transmissiondominant or recessive Autosomal Genetic Disorders • each human has 22 pairs of homologous autosomal chromosomes • 1 set of sex chromosomes – females-homozygous-XX – males-heterozygous-XY • more than 10,000 single gene disorders have been catalogued • autosomal disorders are found in 1 in 500 individuals in general population • affect males & females equally Autosomal Recessive & Dominant Disorders • autosomal recessive disorders – require 2 recessive genes for particular problem • autosomal dominant disorders – require individual has at least one dominant allele • for autosomal dominant disorders at least one parent must be affected • for autosomal recessive disorders parents may or may not have the disorder • parents without disorder are called carriers Autosomal Dominant Disorders • few in number • close to 4,400 known • dominant genes often code for functional or structural proteins – typically affect body structures such as skin, bone, and teeth • everyone bearing gene is affected • Huntington's disease – causes slow progressive deterioration of brain & eventually death Paternal gametes D d d Dd dd Dd dd Maternal gametes d D = mutant gene d = normal gene 2 dd: 2 Dd Autosomal Dominant Disorders • • • • • • • • • expressed in those who have one altered copy of a gene parent has 1 in 2 chance of passing altered gene to offspring with each pregnancy risk remains constant no matter how many affected or unaffected children are born follows predictable patterns of inheritance males & females-equally affected affected individual has an affected parent unaffected individuals do not transmit disorder offspring of affected person mating with a normal mate has 50% change of inheriting disorder rare mating of 2 individuals each with one copy of defective gene has a 75% chance of producing an affected offspring Autosomal Dominant Diseases • Brachydactyly – short fingers & toes • familial hypercholesterolemia, • familial polycystic disease • one type of Alzheimer's disease • hereditary colon cancer • Achondroplasia – dwarfism in which homozygous condition is lethal at embryo stage Autosomal Recessive Disorders • due to recessive allele • manifested only in homozygous genotype • person having heterozygous genotype-Aa is a carrier • estimated-each carry 5-10 recessive lethal genes • most never experienced because have another chromosome with good copy of gene from other parent • recessive defective genes when present in only one copy do not affect owner Autosomal Recessive Disorders • males & females-equally affected • disorder-not apparent in parents or relatives • if individual is affectedboth parents must be carriers • mating of 2 carriers produces 25% chance of producing offspring with disorder • 50% of offspring will be a carrier for the disorder Autosomal Recessive Disorders • recessive conditions that affect humans include • cystic fibrosis • Tay-Sachs disease • beta thalassemia • phenylketonuria • albinism Albinism • group of inherited conditions in which there is little or no pigment in eyes, skin, and hair • individuals have inherited two altered copies of a gene that does not work correctly • does not allow body to make usual amount of melanin • result of lack of tyrosinase • enzyme that catalyzes formation of melanin from tyrosine Cystic Fibrosis • most frequent & common single gene disorder • 5% of white Americans carry defective gene • 1 in 25 persons of European ancestry are carriers Sex Linked Genetic Disorders • more males than women affected • need to acquire only one recessive trait from mother • due to gene on X chromosome Sex linked Disorders Hemophilia Diagnosis • ability to diagnosis improved over last few years • ability to detect exceeds ability to treat • many children with recessive disorders are born to parents who are normal • possible to do carrier testing to determine whether or not someone is a carrier for a particular recessive gene • by determining whether individual is a carrier risks for passing gene to an offspring can be assessed • carrier testing may be considered by individuals who have family history and/or are members of an ethnic group known to be at increased risk for a disorder • Genetic counseling is often recommended prior to carrier testing Fetal Testing • • • • • • • • • • • • techniques are available to test fetus prior to birth Ultra sound non invasive uses sound waves to produce image of fetus used to determine gestational age, fetal position & placenta location cannot detect biochemical or chromosomal abnormalities. Amniocentesis invasion needle inserted into abdomen or vaginafluid is obtainedskin cells of fetus are cultured & harvested & analyzed for abnormal levels of certain substances karyotype can be performed on harvested cells indicating chromosomes present only certain disorders can be detected this way may not provide information until late in pregnancy Amniocentesis Fetal Testing • • • • • • • • • • • • • • Chorionic Villus Sampling tissue removed from chorion – outer membrane of fetal sac can do as early as 8 weeks of gestation cells do not need to be cultured Blood tests conducted on mother 15 to 20 week of pregnancy Alpha fetoprotein (AFP) in mother’s blood may indicate neural tube defects Embryoscopy – direct visualization can be used to detect abnormalities & to treat them can be conducted as early as 1st trimester scope is inserted into uterus often used to diagnose structural abnormalities may be used to treat disorders with gene or stem cell therapy