PATTERNS OF INHERITANCE

14: Mendel and the Gene Idea

14.1: Mendel used the scientific approach to identify two laws of inheritance Mendels Experimental, Quantitative Approach
- Character: a heritable feature that varies among individuals (ex. flower color) -Trait: variant for a character (ex. purple color) -Mendel removed immature stamens of plant, dusted pollen of other plant to flowers, pollinated carpel seed -Used true-breeding (parent produces same as self) plants; typically crossed 2 true-breeding varieties (hybridization) -P generation (parent) F1 generation (first filial) F2 generation(second filial)

The Law of Segregation

-Mendels Experiment: F1=all purple, F2= approx. 3:1 purple:white; concluded heritable factor.gene of recessive trait masked by dominant trait -Alternative versions of genes (alleles) account for variations in inherited characters; DNA sequences at locus can vary slightly -For each character, organism inherits 2 copies of a gene (1 from each parent; also called alleles; each locus represented twice, once on each homolog of pair of chromosomes) -If the 2 alleles at a locus differ, dominant allele determines appearance, recessive allele= no effect -Law of Segregation: 2 alleles for a heritable character segregate during gamete formation and end up in different gametes (an egg/sperm gets only 1 of the alleles present in the somatic cells of the organism making the gamete) -Homozygous: identical alleles; heterozygous: 2 different; phenotype: observable; genotype: genetic -Testcross: breed unknown genotype with recessive homozygote

The Law of Independent Assortment

-Monohybrids: heterozygous for 1 particular character followed in cross -Dihybrids: heterozygous for 2 characters being followed -Alleles segregate independently of each other during gamete formation (ex. YyRr YR, Yr, yR, yr); F2: 9:3:3:1 phenotypic ratio -Law only applies to genes located on different chromosomes/very far apart on same chromosome

14.2: The laws of probability govern Mendelian inheritance The Multiplication and Addition Rules
-Multiplication rule: probability of 1 event x probability of other -Addition rule: probability that any 1 of 2 or more mutually exclusive events will occurs is calculated by adding their individual probabilities

14.3: Inheritance patterns= more complex than predicted by Mendelian genetics Extending Mendelian Genetics for a Single Gene
-Complete dominance: phenotypes of heterozygote and dominant homozygote=indistinguishable -Incomplete dominance: ex. red+white snapdragons= pink F1 b/c heterozygotes have less red pigment than red homozygotes -Co-dominance: 2 alleles each affect phenotype in separate, distinguishable ways (ex. individuals heterozygous for M and N alleles have both M and N molecules on red blood cells, both phenotypes exhibited, not intermediate)

-For any character, dominant/recessive relationship depends on level phenotype is examined (ex. TaySachs disease: brain cells of child cannot metabolize certain lipids b/c crucial enzyme doesnt work properly , organismal level- Tay-Sachs allele=recessive, biochemical level- incomplete dominance b/c heterozygotes show intermediate levels of lipid-metabolizing, molecular level- codominant b/c equal numbers of normal and dysfunctional enzyme molecules can be found) -Multiple alleles: ex. ABO blood group in humans determined by 3 alleles of single gene: IA, IB, i -Pleiotropy: most genes have multiple phenotypic effects

Extending Mendelian Genetics for Two or More Genes

-Epistasis: phenotypic expression of a gene at one locus alters that of a gene at a second locus (ex. gene for pigment deposition-E/e-is epistatic to gene that codes for black/brown pigment-B/b- in Labradors) -Though genes affect same phenotypic character, still follow law of independent assortment -Quantitative characters: vary in population in gradation along a continuum (ex. height, skin color) -Polygenic Inheritance: additive effect of two or more genes on a single phenotypic character

Nature and Nurture: The Environmental Impact on Phenotype

-Genotype associated with norm of reaction (range of phenotypic possibilities due to environmental influences) -Multi-factorial: many factors collectively influence phenotype

14.4: Many human traits follow Mendelian patterns of inheritance Pedigree Analysis
-Pedigree: information about a familys history for a particular trait

Recessively Inherited Disorders

-Heterozygotes usually normal in phenotype b/c one copy of normal allele sufficient amount of specific protein, known as carriers b/c they can transmit recessive allele to offspring -Most people w/ disorder have parents who are both carriers -Cystic fibrosis: most common lethal genetic disease in US, normal allele membrane protein that transports chloride ions, so homozygous recessive high concentration of extracellular chloridemucus that coats certain cells becomes thicker&sticker poor absorption of nutrients, chronic bronchitis, bacterial infections -Sickle-Cell Disease: most common in people of African descent, hemoglobin=abnormal aggregate into long rods that deform red cells into sickle shape when oxygen content=low sickled cells can clump/clog small blood vessels -Normal allele=incompletely dominant at organismal level; carriers have sickle-cell trait, can suffer some symptoms; alleles= codmoninant at molecular level b/c both normal&abnormal hemoglobins are made in heterozygotes -High frequency of heterozygotes b/c single copy of sickle-cell allele reduces frequency of malaria attacks, advantageous in Africa

Dominantly Inherited Disorders

-Heterozygotes usually normal in phenotype b/c one copy of normal allele sufficient amount of specific protein, known as carriers b/c they can transmit recessive -Huntingtons Disease: passed on b/c no obvious phenotypic effect until 35-45 years old

Genetic Testing and Counseling

-Amniocentesis: technique performed in 14th-16th week of pregnancy that can determine whether developing fetus has certain disease -Chorionic villus sampling (CVS): physician inserts narrow tube through cervix into uterus, suctions out tiny sample of tissue from placenta, cells of chorionic villi of placenta have same genotype as individual -A few fetal cells can also be isolated from mothers blood and analyzed

-Some diseases (such as PKU, where child cannot metabolize AA phenylalanine) can be screened for and treated

15: Chromosomal Basis of Inheritance

15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes
-Chromosome theory of inheritance: 1902, Mendelian genes have specific loci (positions) along chromosomes, and chromosomes undergo segregation and independent assortment

Morgans Experimental Evidence: Scientific Inquiry

- Morgan used drosophila melanogaster (fruit fly), convenient b/c of quick breeding time and only 4 pairs of chromosomes (3 autosomes, 1 sex) -Wild type: phenotype for character most commonly observed in natural populations; Morgan got male fly w/ white eyes (mutant phenotype) instead of wild type red eyes -Morgan mated white-eyed male fly w/ red-eyed female F1 offspring w/ red eyesF2 offspring w/ 3:1 ratio but white trait only showed up in males (eye color somehow linked to sex) -Correlation suggested that white-eyed gene was located exclusively on X chromosome (since males only have one X chromosome, then no wild-type allele could be present to mask the recessive allele)

15.2: Sex-linked genes exhibit unique patterns of inheritance The Chromosomal Basis of Sex
- Y chromosome is much shorter than X and only short segments at either end are homologous w/ corresponding regions of X -Anatomical signs of sex begin when embryo is about 2 mo. old; sex determining region of Y chromosome is needed for development of testes (absence of SRY ovaries)

-Sex-linked gene: located on either sex chromosome

Inheritance of X-Linked Genes

- Hemizygous: used to describe X-linked trait for males, any male receiving recessive allele from mother will express trait so many more males have x-linked recessive disorders -Duchenne muscular dystrophy: progressive weakening of muscles and loss of coordination, absence of key muscle protein dystrophin linked to specific locus on X chromosome -Hemophilia: X-linked recessive disorder defined by absence of 1 or > proteins needed for blood clotting

X Inactivation in Female Mammals

- Most of 1 X chromosome in each cell of female mammals inactive during early embryonic development condenses into Barr body--> reactivated in cells that give rise to eggs -Since selection of which X chromosome will form Barr body= random and independent, females consist of mosaic of 2 types of cells (some have active X from father, some from mother) -Ex. mosaicism: recessive X-linked mutation can prevent development of sweat glands, but woman who is heterozygous has patches of normal skin and patches of skin lacking sweat glands -Inactivation involves modification of DNA and histone proteins bound to it (attachment of --CH/methyl groups to nitrogenous bases) -Specific region of each X chromosome interact w/ each other at early stage of embryonic developmentX-inactive specific transcript/XIST becomes active only on chromosome that will become Barr bodyRNA product of this gene attach to X chromosome, almost covering it

15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome How Linkage Affects Inheritance

- Morgans experiment crossing wild type flies w/ gray body and normal wings with double mutants w/ black body and vestigial wings higher proportion of combo of traits seen in P generation flies than would be expected if genes assorted independently so genes are linked -However, combos not seen in P generation were also produced, so not always linked genetically b/c of genetic recombination: production of offspring w/ combos of traits that differ from parents

Genetic Recombination and Linkage

-Recombination of Unlinked Genes- Independent Assortment of Chromosomes -Parental types: offspring that match either of P generation phenotypes; recombinant types: offspring w/ new combos -Physical basis of recombination between unlinked genes is random orientation of homologous chromosomes at metaphase I of meiosis -Recombination of Linked Genes- Crossing Over -Crossing over: breaks physical connection between specific alleles on same chromosome, occurs while replicated homologous chromosomes are paired during prophase of meiosis I, end portions of 2 non-sister chromatids trade places

Mapping the Distance Between Genes Using Recombination Data

-Genetic map: ordered list of genetic loci along a particular chromosome -Sturtevant hypothesized: recombination frequency depends on distance between genes on a chromosome, farther apart 2 genes are higher probability crossover will occur -Linkage map: genetic map based on recombination frequencies; Sturtevant expressed distances between genes in map units (1 map unit=1% recombination frequency) -Observed frequency of recombination in crosses w/ genes so far from each other that crossover= virtually certain is 50%, which is indistinguishable from genes on different chromosomes (genes on same chromosome can act as though genetically unlinked) -Linkage maps are only approx. b/c frequency of crossing over is not uniform as Sturtevant assumed -Cytogenetic maps: locate genes w/ respect to chromosomal features like stained bands

15.4: Alterations of chromosome # or structure cause some genetic disorders Abnormal Chromosome Number
-Nondisjunction: members of a pair of homologous chromosomes dont move apart properly during meiosis I or sister chromatids fail to separate during meiosis II (1 gamete receives 2 of the same type of chromosome and another gamete receives none) -Aneuploidy: abnormal number of a particular chromosome; monosomic: 2n-1 chromosomes; trisomic: 2n+1 chromosomes; polyploidy: more than 2 complete chromosome sets in all somatic cells

Alterations of Chromosome Structure

-Deletion: chromosomal fragment is lost; duplication: if deleted fragment becomes attached as extra segment to sister chromatid; inversion: fragment reattaches to original chromosome in reverse orientation; translocation: fragment joins nonhomologous chromosome

Human Disorders Due to Chromosomal Alterations

-Down syndrome/ Trisomy 21: extra chromosome 21 (47 total) -Aneuploidy of sex chromosomes: Klinefelter syndrome= extra X chromosome (small testes, sterile, female body characteristics common), Turner syndrome= monosomy X (sterile) -Cri du chat: deletion of chromosome 5, usually die as child, severely intellectually disabled -Chronic myelogenous leukemia: reciprocal translocation happens during mitosis of cells that will become white blood cells (exchange of large part of 22 with tip of 9 produces Philadelphia chromosome

15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance

Genomic Imprinting
-Genomic imprinting: variation in phenotype depending on whether allele is inherited from male or female parent, occurs during gamete formation and results in silencing of particular allele of certain genes -Usually consists of methyl (-CH) added to cytosine nucleotides of one of the alleles (usually silences, sometimes activates)

Inheritance of Organelle Genes

-There are extranuclear genes and cytoplasmic genes; mitochondria, chloroplasts, plastics contain small circular DNA molecules