Chapter 15: The Chromosomal Basis of Inheritance

Essential Knowledge 3.a.4 – The inheritance pattern of many traits cannot be explained by simple Mendelian genetics (15.1, 15.2, 15.3, 15.5). 3.c.1 – Changes in genotype can result in changes in phenotype (15.4).

Sutton (1902) Developed the “Chromosome Theory of Inheritance” 1) Mendelian factors or alleles are located on chromosomes 2) Chromosomes segregate and show independent assortment

Morgan Embryologist at Columbia University Chose to use fruit flies as a test organism in genetics Allowed the first tracing of traits to specific chromosomes

Fruit Fly Drosophila melanogaster Feeds on fungus growing on fruit Early test organism for genetic studies

Reasons he chose fruit fly Small Cheap to house and feed Short generation time New generation every 2 weeks 100s of offspring produced Few chromosomes 4 pairs (8 total) 3 pairs autosomes, 1 pair sex

Genetic Symbols Mendel: use of uppercase or lowercase letters T = tall t = short Morgan: symbol from the mutant phenotype + = wild phenotype (natural pheno) No symbol = mutant phenotype (any pheno different from wild)

Examples Recessive mutation: w = white eyes w+ = red eyes Dominant mutation: Cy = Curly wings Cy+ = Normal wings Letters come from 1st mutant trait observed

Morgan Observed: Same as Mendel’s F1 A male fly with a mutation for white eyes Then, he crossed the white eye male with normal red eye female All had red eyes Same as Mendel’s F1 This suggests that white eyes is a genetic recessive

F1 X F1 = F2 Morgan expected the F2 to have a 3:1 ratio of red:white He got this ratio However, all of the white eyed flies were MALE Most red eyed flies were FEMALE Therefore, the eye color trait appeared to be linked to sex

Morgan discovered: Sex-linked traits Genetic traits whose expression are dependent on the sex of the individual Genes on sex chromosomes exhibited unique patterns

Eye color gene located on X chromo (with no corresponding gene on Y)

Morgan Discovered There are many genes, but only a few chromosomes Therefore, each chromosome must carry a number of genes together as a “package” There was a correlation between a particular trait and an individual’s sex

Linked Genes Traits that are located on the same chromosome (that tend to be inherited together) Result: Failure of (deviation from) Mendel's Law of Independent Assortment. Ratios mimic monohybrid crosses.

Body Color and Wing type

Body color and wing type Wild: gray and normal (dom +) Mutant: Black and vestigal (rec) This is why we use “b” for body color alleles and “vg” for wing alleles Symbols: Body color - b+: gray; b: black Wings - vg+: normal; vg: vestigal

b+b vg+vg X bb vgvg Example #1: b+b = gray; vg+vg = normal #2: bb = black; vgvg = vestigal (b+ linked to vg+) (b linked to vg) If unlinked: 1:1:1:1 ratio. If linked: ratio will be altered

Crossing-Over Occurs during Pro I of meiosis Breaks up linkages and creates new ones Recombinant offspring formed that doesn't match the parental types

If Genes are Linked: Independent Assortment of traits fails Linkage may be “strong” or “weak”

Linkage Strength Weak - farther apart Strong - closer together Degree of strength related to how close the traits are on the chromosome Weak - farther apart Strong - closer together Usually located closer to centromere

Genetic Maps Constructed from crossing-over frequencies 1 map unit = 1% recombination frequency Have been constructed for many traits in fruit flies, humans and other organism.

Sex Linkage in Biology Several systems are known: Mammals – XX and XY Diploid insects – X and XX Birds – ZZ and ZW Haploid-Diploid

Sex Linkage in Biology Mammals Diploid insects Birds Haploid-Diploid Determined by whether sperm has X or Y Diploid insects Only X chromosomes present Birds Egg determines sex Haploid-Diploid Females develop from fert egg Males develop from unfert egg

Chromosomal Basis of Sex in Humans Sex determination ALWAYS 50-50 X chromosome - medium sized chromosome with a large number of traits Y chromosome - much smaller chromosome with only a few traits

Human Chromosome Sex Eggs – only contain X Sperm – either X or Y Males - XY Females - XX Comment - The X and Y chromosomes are a homologous pair, but only for a small region at one tip

Sex Linkage Inheritance of traits on the sex chromosomes NOT TO BE CONFUSED WITH sex-linked traits!!!!! X Linkage - common; Y- rare Dads: only to daughters (b/c dads ONLY give X chromo to daughters) Moms: to either sex

Males Hemizygous - 1 copy of X chromosome Show ALL X traits (dominant or recessive) More likely to show X recessive gene problems than females

X-linked Disorders and Patterns Disorders on X-chromo: Color blindness Duchenne's Muscular Dystrophy Hemophilia (types a and b) Patterns Trait is usually passed from a carrier mother to 1 of 2 sons Affected father has no affected sons, but passes the trait on to all daughters (who will be carriers for the trait)

Comment Watch how questions with sex linkage are phrased: Chance of children? Chance of males? Chance of females? You MUST practice genetics problems w/ these traits: Hemophilia, Muscular dystrophy and colorblindness (they all work the same!)

Can Females be color-blind? Yes!!! ONLY if their mother was a carrier and their father is affected How? Mother contributes X (with affected allele) and dad contributes all he can to make a daughter – affected X

25 29 Are you color blind? 45 56 6 8

Y-linkage Hairy ear pinnae Comment - new techniques have found a number of Y-linked factors that can be shown to run in the males of a family Ex: Jewish priests

Sex Limited Traits Traits that are only expressed in one sex Ex: prostate development, gonad specialization, fallopian tube development

Sex Influenced Traits Traits whose expression differs because of the hormones of the sex Ex: beards, mammary gland development, baldness Baldness: Testosterone – makes the trait act as a dominant No testosterone – makes the trait act as a recessive Males – have gene = bald Females – must be homozygous to have thin hair (rare)

X chromosome inactivation In every somatic cell (in females), one X chromosome is inactivated Humans: differs/random Kangaroos: always paternal X that is inactivated Called Barr bodies

Barr Body Inactive X chromosome observed in the nucleus Becomes inactive during embryonic development Way of determining genetic sex (without doing a karyotype)

Barr body description Compact body which lies close to nuclear envelope Most genes on this X are NOT expressed Inside developed ovaries, these are reactivated (so that each ova will get an active X)

Lyon Hypothesis Which X inactivated is random Inactivation happens early in embryo development by adding CH3 groups to the DNA Changes DNA nucleotide Result - body cells are a mosaic/combo of X types Some have active X from mom, others active X from dad

Examples Calico Cats Human examples are known (sweat gland disorder)

Question? Why don’t you find many calico males? They must be XB XOY and are always sterile Why? They MUST have an extra X chromo (to have an inactive X - you must have TWO!)

Chromosomal Alterations Two types of alterations: Changes in number Changes in structure

Number Alterations Aneuploidy - too many or too few chromosomes, but not a whole “set” change Polyploidy - changes in whole “sets” of chromosomes

Aneuploidy Caused by nondisjunction the failure of a pair of chromosomes to separate during meiosis Result: too many or too few chromosomes in a gamete Nondisjunction in Meiosis I produces 4 abnormal gametes. Nondisjunction in Meiosis II produces 2 normal and 2 abnormal gametes.

Types of Aneuoploidy Monosomy: 2N – 1 (very rare) Mono = one (missing copy) Trisomy: 2N + 1 (more common) Tri = three (extra copy) Normal: 2N

Turner Syndrome Monosomy 2N - 1 or 45 chromosomes Genotype: X_ or X0 Phenotype: female, but very poor secondary sexual development. Characteristics: Short stature. Extra skin on neck. Broad chest. Usually sterile Normal mental development except for some spatial problems.

Question Why are Turner Individuals usually sterile? Odd chromosome number Two X chromosomes needed for ovary development.

Other Sex Chromosome changes Kleinfelter Syndrome Meta female Supermale

Kleinfelter Syndrome Trisomy 2N + 1 (2N + 2, 2N + 3) Genotype: XXY (XXXY, XXXXY) Phenotype: male, sexual development may be poor/slow Often taller than average, mental development fine (in XXY), usually sterile More X = more mental problems

George Washington May have been a Kleinfelter Syndrome individual. Much taller than average Produced no children/sterile individual

Meta female Trisomy 2N + 1 or 2N + 2 Genotype: XXX or XXXX Phenotype: female, but sexual development poor. Mental impairment common.

XYY Syndrome OR Super male Trisomy 2N + 1 or 2N + 2 Genotype: XYY or XYYY Phenotype: male, usually normal development, fertile w/ normal sex organ development

Trisomy events Trisomy 21: Down Syndrome Trisomy 13: Patau Syndrome Both have various physical and mental changes

Down’s

Down’s Syndrome Increases with maternal age (especially above 35) How? An embryo’s ovaries are halted in meiosis I (during egg development) When ovulation occurs, the eggs resume meiosis and nondisjunction occurs then This is why it is often seen more in older women Mental retardation Heart defects Characteristic facial features

Patau

Question? Why is trisomy more common than monosomy? Fetus can survive an extra copy of a chromosome, but being hemizygous for somatic cell is usually fatal Why is trisomy 21 more common in older mothers? Maternal age increases risk of nondisjunction

Polyploid Triploid= 3N Tetraploid= 4N Usually fatal in animals Cells receive AN ENTIRE EXTRA COPY of all homologous chromosomes (including sex chromo)

Question? In plants, even # polyploids are often fertile, while odd # polyploids are sterile. Why? Odd number of chromosomes can’t be split during meiosis to make spores.

Chromosome Structure Alterations Deletions: loss of genetic info Duplications: extra copies of genetic info Inversions and translocations: Position effects: a gene's expression is influenced by its location to other genes

Cri Du Chat Syndrome Part of p arm of #5 missing Deletion chromosomal abnormality Good survival rate Severe mental retardation Small sized heads common Malformed larynx w/ vocal/speech problems

Cri du chat

Fragile X Part of X chromo is missing Sterile Mental retardation Deletion Sterile Mental retardation Oversized testes (if male); ovaries (if female) “Double jointedness”

Philadelphia Chromosome Caused by translocation An abnormal chromosome produced by an exchange of portions of chromosomes 9 and 22 Causes chronic myeloid leukemia

Parental Imprinting of Genes Gene expression and inheritance depends on which parent passed on the gene Usually caused by different methylations of the DNA CAUSE: Imprints are "erased" in gamete producing cells and re-coded by the body according to its sex RESULT: Phenotypes don't follow Mendelian Inheritance patterns because the sex of the parent does matter

Example: Both lack a small gene region from chromosome 15 Prader-Willi Syndrome and Angelman Syndrome Both lack a small gene region from chromosome 15 Male gene contribution missing: Prader-Willi Female: Angelman

Why have parental imprinting? Method that cells might use to detect that TWO different sets of chromosomes are in the zygote

Extranuclear Inheritance Inheritance of genes not located on the nuclear DNA Where does it come from? DNA in organelles (Mitochondria and chloroplasts) Result: Mendelian inheritance patterns fail. Maternal Inheritance of traits where the trait is passed directly through the egg to the offspring

Mitochondria Myoclonic Epilepsy Ragged Red-fiber Disease Leber’s Optic Neuropathy All are associated with ATP generation problems and affect organs with high ATP demands Muscle, brain

Chloroplasts Gives non-green areas in leaves Called variegation Several different types known Very common in ornamental plants

Examples

Summary Recognize the relationships between Mendelian inheritance patterns and chromosomes. Identify linked genes and their effect on inheritance patterns. Recognize the chromosomal basis of recombination in unlinked and linked genes. Recognize how crossover data is used to construct a genetic map. Identify the chromosomal basis of sex in humans. Recognize examples of sex-linked disorders in humans.

Summary Continued Identify X-inactivation and its effect in females. Recognize sources and examples of chromosomal alterations in humans. Identify examples of abnormalities in sex chromosome number in humans. Recognize the basis and effects of parental imprinting of genes in human inheritance patterns. Recognize the basis and effect of extranuclear inheritance on genetic inheritance patterns.