Week 5: Ch 5 (7,12): Chromosome Mapping in Eukaryotes

Chromosomes are the unit of transmission in meiosis, not genes

________ can not undergo independent assortment

Frequency of ________ on a single chromosome is proportional to distance between them

Crossing over results in ______

_______: indicate relative location of genes on chromosome

• Linked genes

• crossing over

• recombination

• Chromosome maps

Genes Linked on the Same Chromosome Segregate ______.

• Together

______ consequences

– Independent assortment (No linkage exhibited)

– Linkage without crossing over (_______)

– Linkage with crossing over (Generates recombinant (crossover) gametes)

• Meiotic

• Complete linkage

_______

– No crossing over between two genes

– Produces ——— (noncrossover) gametes

_______

– Occurs between two nonsister chromatids

– Both parental and recombinant (crossover) gametes are produced

• Complete linkage

• parental

• Crossing over

_______

– Complete linkage between two genes due to close proximity

– Unique F2 phenotypic ratio results

_______

– Genes on the same chromosome are part of this

– Number of linkage groups should correspond to haploid number of chromosomes

• Linkage ratio

• Linkage group

Crossing Over Serves as the Basis for Determining the ______ between Genes in Chromosome Mapping

• Distance

______

– Synapsed chromosomes in meiosis wrap around each other

– X-shaped intersections with points of overlap

▪ Points of genetic exchange

• Chiasmata

Two genes located close to each other along a chromosome are less likely to have _____.

• chiasma

Sturtevant

– Compiled data from crosses

– Recombination frequencies between linked genes are ______

– Frequency of exchange is estimate of relative distance between two genes

• additive

______

– 1 percent recombination between two genes on chromosome

– Also called ______

– Relative distances, not exact ones

• Map unit (mu)

• centi-Morgans (cM)

_______

– Occurs between two nonsister chromatids

– Recombination is observed in 50 percent of gametes

– In genes 50 map units apart, crossing over can be expected between 100 percent of tetrads

• Single crossover (SCO)

SCO is _____ between two nonsister chromatids in tetrad stage

– ______ gametes produced

– ______ gametes produced

• Single exchange

• Two noncrossover (parental)

• Two crossover (recombinant)

_____ crossover

– Used to determine distance between two linked genes

_____ crossover

– Double exchanges of genetic material

– Used to determine distance between three linked genes

– Genes must be _____ for two alleles

• Single

• Double

• heterozygous

Three criteria of three-point mapping:

– Parent must be heterozygous for all three genes under consideration

– Phenotypic class must reflect genotype of gametes of parents

– Sufficient number of offspring must be produced for representative sample

______ phenotypes

– Occur in greatest proportion of offspring

______ phenotypes

– Occur in the smallest proportion

• Noncrossover F2

• Double-crossover (DCO)

_____ classes of phenotypes

– F2 phenotypes complement each other

▪ Derived from heterozygote

▪ Have wild type and mutant for all three genes

• Reciprocal

Determining gene sequence:

– Method 1 based on ______

– Method 2 uses _____ and Also considers _____

• three possible arrangements of genes

• three possible arrangements

• double-crossover event

As the Distance between Two Genes Increases, Mapping Estimates Become _____.

• More Inaccurate

_______

– Inhibition of further crossover events

– Inhibited by another crossover event nearby

– Reduces expected number of multiple crossovers

• Interference

• Interference: I = 1 − C

______: Calculated to quantify disparities that result from interference

• Coefficient of coincidence (C)

• 

Interference

– _____ when no double crossovers occur

– _____: Fewer double-crossover events than expected occur

▪ I is a positive number

– ______: More double-crossover events than expected occur

▪ I is a negative number

• Complete

• Positive

• Negative

Large number of mutants in organisms such as

– ______

• Allows for construction of extensive chromosome mapping

• Drosophila

_______

– Relies on probability calculations

– Demonstrates linkage between two genes when linkage analysis relies primarily on pedigrees

– Assesses probability that pedigree with two traits reflects genetic linkage between them

Lod score method

________

– Made possible the assigning of human genes to their respective chromosomes

– Involves fusing two cells into a single hybrid cell: ______

• Somatic cell hybridization

• heterokaryon

________:

– Heterokaryons cultured in vivo—nuclei are fused together

• Synkaryon

________

– Presence or absence of each chromosome, with presence or absence of each gene product

– Four gene products tested in relation to eight human chromosomes

• Synteny testing

_______

– Short segments of DNA with known sequence and location

– Useful landmarks for mapping

– Earliest examples of DNA markers:

• DNA markers

• RFLPs and microsatellites

RFLPs: ____-___

– Polymorphic sites

– Generated when specific DNA sequences are recognized and cut by restriction enzyme

• Microsatellites

– Short repetitive sequences

– Found throughout genome

• Restriction fragment length polymorphisms

SNPs: _______

– Found throughout genome

– Used by geneticists to identify and locate related genes

– Used to screen for diseases

▪ Example: ______

• Single-nucleotide polymorphisms

• Cystic fibrosis

________

– Gene located by using DNA markers

– Life-shortening autosomal recessive exocrine disorder

– Gene causing disorder found on chromosome 7

• Cystic fibrosis

Genetic mapping techniques used to study relationship between _______.

• Mapping in maize

– Used ________

– Established crossing over involves a physical exchange of chromosome regions

• chiasmata and crossing over

• cytological markers

_______ occur during mitosis but do not produce new allelic combinations.

• Sister chromatid exchanges (SCEs)

________

– Reciprocal exchanges similar to crossing over

– Between sister chromatids (crossing over is between NONsisters)

_______ chromosomes

– Sister chromatids involved in mitotic exchanges

– Patch-like appearance when stained and viewed under a microscope

• SCEs: Sister chromatid exchanges

• Harlequin

Agents that induce chromosome damage

– ________

– Increase frequency of sister chromatid exchange in Bloom syndrome

______

– Human disorder

– Caused by mutation in ______ chromosome 15

– Prenatal and postnatal retardation of growth

– Excessive SCEs

– Many translocations

• Viruses, X-rays, UV, mutagens

• Bloom syndrome

• BLM gene

BLM gene

– Encodes enzyme ______

– DNA helicase’s known role is _____

– Not known how it causes ______

• DNA helicase

• DNA replication

• Bloom Syndrome

In animals, including humans, differentiation of sexes is evident via _____

_____ chromosomes

– Dissimilar

– Example: Sex chromosomes X and Y

________

– Characterize one sex or the other in a wide range of species

________

– By specific genes not entire chromosomes

• phenotypic dimorphism

• Heteromorphic

• Sex chromosomes

• Sex determination

Mode of sex determination: _____

– _____ of sex determination

– Depends on random distribution of X chromosome into half of male gametes

– Presence of _____ chromosomes in zygote results in female offspring

– Presence of _____ chromosome results in male offspring

• Protenor

• XX/XO mode

• two X

• one X

______ of sex determination

– ______ of sex determination

– Female gametes have one X chromosome

– Male gametes have either an X or Y chromosome

• Lygaeus mode

• XX/XY mode

_____ sex

– Producing like chromosomes

– Zygotes with two X chromosomes

– Results in female offspring

______ sex

– Producing unlike chromosomes

– Zygotes with one X and one Y chromosome

– Results in male offspring

• Homogametic

• Heterogametic

Females as ______ sex

–_______ sex determination

– Females are the heterogametic (ZW) sex

– Males are the homogametic (ZZ) sex

– Example: Chickens

• heterogametic

• ZZ/ZW

_______ determines maleness

– Human karyotype

▪ 22 pairs of autosomal chromosomes

▪ 2 sex chromosomes

▪ Reveals one pair of chromosomes differs in males

and females

– Females: XX

– Males: XY

• Y chromosome

______ syndrome

– Two human abnormalities

– Characterized by aberrant sexual development

– Both syndromes result from _____

▪ Failure of X chromosomes to segregate during meiosis

• Klinefelter and Turner

• nondisjunction

________

– Tall, long arms and legs

– Large hands and feet

– Internal ducts are male, rudimentary testes fail to produce sperm

– Feminine development not suppressed

▪ Enlarged breasts common, rounded hips

• Klinefelter syndrome (47,XXY)

______

– Phenotypically female

▪ Female external genitalia and internal ducts

▪ Ovaries are rudimentary

▪ Underdeveloped breasts

– Short stature

– Cognitive impairment

• Turner syndrome (45,X)

_________

– Three X chromosomes

– Normal set of autosomes

– Results in female differentiation

– Sometimes women are perfectly normal

– Sometimes underdeveloped secondary sex characteristics occur

▪ Sterility and mental retardation

-47,XXX syndrome: Triplo-X

_______

– Only consistently shared characteristic—males are over 6 feet tall

– Subnormal intelligence

– Personality disorders

• 47,XYY condition

_______

– The tissues that will form the gonad

By the fifth week of gestation, a pair of gonadal (genital) ridges associated with each embryonic kidney

Gonadal phenotype is sexually indifferent

– Primordial germ cells migrate to ridges

_______

– Gonadal ridges can form either ovaries or testes

• Gonadal primordia

• Bipotential gonads

Y chromosome and male development

– Y chromosome has at least ____ genes

– _____ genes than X chromosome (100 genes)

PARs: Pseudoautosomal regions

– Present on both ends of Y chromosome

– Share homology with regions on X chromosome

– Synapse and recombine with X during meiosis

• 50

• Fewer

Pairing region critical to segregation of X and Y chromosomes during male gametogenesis

_________

– Nonrecombining region of Y chromosome

_______

– Located adjacent to PAR of the short arm of Y chromosome

– Controls male development

– Encodes protein: ______

• MSY: Male-specific region of the Y

• SRY: Sex-determining region Y

• Testis-determining factor (TDF)

TDF: Testis-determining factor

– At 6–8 weeks of development, _____ gene becomes active in XY embryos

– Encodes protein that triggers testes formation

• SRY

MSY: Male-specific region Y

23 million base pairs

Divided into three regions

– _______ region (15 percent of MSY)

– ________ region (20 percent)

– _______ region (30 percent)

▪ Encodes proteins specific to development and function of testis

• X-transposed

• X-degenerative

• Ampliconic

_______

– Genetic mechanism

– Balances dose of X chromosome gene expression in males and females

– Prevents excessive expression of X-linked genes in humans and other mammals

• Dosage compensation

________

– Genetic mechanism compensates for X dosage disparities

– Inactive X chromosome, highly condensed

– Darkly stained body in interphase nerve cells observed: _____

– Random inactivation

– Occurs early in embryonic development

• Barr bodies (sex chromatin bodies)

• Barr bodies

______

– Explains dosage compensation

– Follows N − 1 rule (N = total number of X chromosomes)

– Then why do we have Turner and Kleinfelter syndromes?

• X-inactivation

Why does X-inactivation not affect syndromes such as Turner or Klinefelter?

– Chromosome inactivation not in early stages of development for cells destined for gonadal tissue

– Not all X chromosomes forming Barr bodies are inactivated

▪ 15% escape inactivation

______

– Glucose-6-phosphate dehydrogenase

– Synthesis of G6PD enzyme controlled by X-linked gene

– Experiment with G6PD mutants provides strong support of Lyon hypothesis

▪ Random permanent inactivation of X chromosome

• G6PD

______

– Active only on inactive X

– Has ______ gene critical for X-inactivation

– Two noncoding genes in ____ locus

▪ _____ play important roles in X chromosome inactivation

• Xic: X inactivation center

• X-inactive specific transcript (XIST)

• Xic

• Tsix and Xite

_____

– At interphase, eukaryotic chromosomes uncoil and decondense into a form called chromatin

– During interphase, chromatin is dispersed throughout nucleus

– During cell division, chromatin coils and condenses back into visible chromosomes

Chromatin

______

– Positively charged proteins associated with chromosomal DNA in eukaryotes

– Contain large amounts of lysine and arginine

– Makes electrostatic bonding to negatively charged phosphate possible

• Five main types of histones

– H1, H2A, H2B, H3, and H4

• Histones

_____

– Electron microscopic observations of chromatin revealed fibers composed of linear array of these spherical particles

– Resemble beads on a string

– Are condensed several times to form intact chromatids

• Nucleosomes

_____

– Resemble beads on a string

– Are condensed several times to form intact chromatids

• Nucleosomes

Twists and turns of DNA ____ encircle histones

Principal packaging unit of DNA in eukaryotic nucleus

Unstructured _____ are not packed into folded histone domains within nucleosome

– Tails devoid of secondary structure protrude through minor groove

• superhelix

• histone tails

_______ are important to genetic function

• Histone tails provide potential targets along chromatin fiber for chemical modifications

______

• Chemical modifications

• – Acetylation

  – Methylation

  – Phosphorylation

_______

– Enzyme histone acetyltransferase (HAT)

– Addition of acetyl group to positively charged amino group on side chain (lysine) changes net charge of protein by neutralizing positive charge

Acetylation

_____

– Enzyme methyltransferase

– Adds methyl groups to arginine and lysine residues in histones

– Positive correlation with gene activity

Methylation

______ of the nitrogenous base cytosine within polynucleotide chains of DNA

– Forms 5-methyl cytosine

– Usually negatively correlated with gene activity

• Methylation

______

– Region of DNA where many cytosine guanine dinucleotides are present

• CpG island

______

– Uncoiled and active

– Appears unstained during interphase

______

– Condensed areas are mostly inactive

– Appears stained during interphase

• Euchromatin

• Heterochromatin

_______

– Genetically ______: lacks genes or contains repressed genes

– Replicates later in S phase than euchromatin

– Telomere maintains chromosome integrity

– Centromere involved in chromosome movement

• Heterochromatin

• inactive