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 chromosomes2) 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 melanogasterFeeds on fungus growing on fruitEarly test organism for genetic

studies

Reasons he chose fruit fly

Small Cheap to house and feedShort generation time

New generation every 2 weeks100s of offspring producedFew 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:

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

Example

b+b vg+vg X bb vgvg#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

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:1. Mammals – XX and XY2. Diploid insects – X and XX3. Birds – ZZ and ZW4. Haploid-Diploid

Sex Linkage in Biology

1. Mammals Determined by whether sperm has X or Y

2. Diploid insects Only X chromosomes present

3. Birds Egg determines sex

4. 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 XSperm – either X or Y

Males - XYFemales - 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 PatternsDisorders 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

Are you color blind?

25

45

29

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 SyndromeTrisomy2N + 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 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:

Prader-Willi Syndrome and Angelman SyndromeBoth lack a small gene region from chromosome 15

Male gene contribution missing: Prader-WilliFemale: 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.