Http:// AP BIOLOGY Chapter 15 Chromosomal Basis of Inheritance Big Idea 3: Living systems

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AP BIOLOGYChapter 15

Chromosomal Basis of Inheritance

Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes.

Essential knowledge 3.A.3: The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring. a. Rules of probability can be applied to analyze passage of single gene traits from parent to offspring.

GENOTYPE TT = 25% Tt = 50 % tt = 25%

PHENOTYPE 75% dominant trait 25% recessive trait

Punnett by Riedell

AaBbCcDD

Probability of aBcD

½ x ½ x ½ x 1 =1/8

Essential knowledge 3.A.3. b. Segregation and independent assortment of chromosomes result in genetic variation.

Evidence of student learning is a demonstrated understanding of each of the following: 1. Segregation and independent assortment can be applied to genes that are on different chromosomes.

~ The behavior of chromosomes during meiosis accounts for Mendel’s laws of segregation and independent assortment

http://bioap.wikispaces.com/file/view/crossing_over.gif/133299913/238x238/crossing_over.gifhttp://bio1151.nicerweb.com/Locked/media/ch14/14_08IndependentAssort.jpg

Essential knowledge 3.A.3. b. Segregation and independent assortment of chromosomes result in genetic variation. Evidence of student learning isa demonstrated understandingof the following: 1. Segregation and independent assortment can be applied to genes that are on different chromosomes.

http://bio1151.nicerweb.com/Locked/media/ch14/14_08IndependentAssort.jpg

Essential knowledge 3.A.3. b. Segregation and independent assortment of chromosomes result in genetic variation.

Evidence of student learning is a demonstrated understanding of each of the following: 2. Genes that are adjacent and close to each other on the same chromosome tend to move as a unit;

the probability that genes will segregate as a unit is a function of the distance between them.

http://anthro.palomar.edu/biobasis/images/linked_genes.gifhttp://cnx.org/content/m47304/latest/Figure_08_03_06.jpg

The farther apart genes are on a chromosome the more likely they are to be separated during crossing over

Mutant phenotypesShort aristae

Black body

Cinnabareyes

Vestigialwings

Brown eyes

Long aristae(appendageson head)

Gray body

Redeyes

Normalwings

Redeyes

Wild-type phenotypes

IIY

IX IV

III

0 48.5 57.5 67.0 104.5

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Many fruit fly genes were mapped initially using recombination frequencies

T.H. Morgan did experiments with fruit flies to see how linkage affects the inheritance of two different characters ~ Linked genes that are close together on the same chromosome do not assort independently ~ Genes that assort independently are either:

- on separate chromosomes OR - are far apart on the same chromosome

Linkage Mapping: Using Recombination Data •Cross true breeding parents of different phenotypes

•Cross heterozygous F1 organisms with pure-breeding recessives (like a TEST CROSS)

• Count recombinants (ones that look different from parental phenotype)

male flies with white eyesfemale flies with red eyes (wild type)

The F1 generation all had red eyes

F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes

T.H. Morgan proposed that the white eye mutation was carried on X chromosome

Essential knowledge 3.A.3.bEvidence of student learning is a demonstrated understanding of each of the following: 3. The pattern of inheritance (monohybrid, dihybrid, sex-linked, and genes linked on the same homologous chromosome) can often be predicted from data that gives the parent genotype/ phenotype and/or the offspring phenotypes/genotypes.

Essential knowledge 3.A.4: The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. a. Many traits are the product of multiple genes and/or physiological processes.

Evidence of student learning is a demonstrated understanding of the following: 1. Patterns of inheritance of many traits do not follow ratios predicted by Mendel’s Laws and can be identified by quantitative analysis, where observed phenotypic ratios statistically differ from the predicted ratios.

22 +XX

22 +X

76 +ZZ

76 +ZW

16(Haploid)

16(Diploid)

(b) The X–0 system

(c) The Z–W system

(d) The haplo-diploid system

Different systems of sex determinationare found in other organisms

Temperature determination- some reptiles

Essential knowledge 3.A.4: The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. b. Some traits are determined by genes on sex chromosomes.

To foster student understanding of this concept, instructors can choose an illustrative example such as:

• Sex-linked genes reside on sex chromosomes (X in humans). • In mammals and flies, the Y chromosome is very small and carries few genes. • In mammals and flies, females are XX and males are XY; as such, X-linked recessive traits are always expressed in males.

Y chromosome-small & carries only a few genes

Y linked traits show up ONLY in MALES

EX: hairy pinna

SRY geneMaster control geneturns on other genesCreates a cascade of activationto make developing embryo into a MALEhttp://www.nature.com/scitable/content/18935/pierce_4_10_large_2.jpg

http://pageofmystery.com/ALPHAS/genetics/earhairbig.jpg

http://gizmodo.com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306.php

Recessive genes carried on the X chromosome

X-Linked Genes

Red-green colorblindnessMutation in protein receptors in eye that distinguish colors

HemophiliaInability to make blood clotting factors

Duchenne Muscular Dystrophy Change in muscle proteins; results early death

X-linked traits show up more frequently in males

The X chromosome in males . . .

flies WITHOUT a copilot!

What’s the pattern:

X-LINKED RECESSIVE traits ~ Show up more frequently in males

because they have no back up X ~ Females need two recessive alleles to

show the trait. ~ Females can be carriers for X linked traits ~ Male can never be carriers of X linked recessive traits

AUTOSOMAL RECESSIVE traits ~ Both males and females can be carriers for autosomal recessive traits.

Essential knowledge 3.A.4. The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. • Some traits are sex limited • Expression depends on the sex of the individual Ex: milk production in female mammals pattern baldness in males.

MALE PATTERN BALDNESSSEX LIMITED (SEX INFLUENCED)

AUTOSOMAL-NOT ON A SEX CHROMOSOME BUT . . . SHOWS DIFFERENT PATTERN IN MALES & FEMALES

MALESBB or Bb = baldbb= not bald

FEMALESBB = baldBb or bb= not bald

Almost like B is dominant in malesand b is dominant in females

Essential knowledge 3.A.3: The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring.

c. Certain human genetic disorders can be attributed to the inheritance of single gene traits or specific chromosomal changes, such as nondisjunction. To foster student understanding of this concept, instructors can choose an illustrative example such as: • Sickle cell anemia • Tay-Sachs disease • Huntington's disease • X-linked color blindness • Trisomy 21/Down syndrome • Klinefelter syndrome

AUTOSOMAL RECESSIVEPhenylketonuria-PKUEnzyme to break down phenylalanine is missingBuild up in brain causes mental retardationNeed diet low in proteins

TAY SACHSLysosomal storage disorderFats aren’t broken down; build up in brainCause blindness, retardation; early deathMore common in Jewish populations

CYSTIC FIBROSISMutation in gene for Cl- ion transportBuild up of mucous in body organsDigestive/respiratory problemsMore common in Caucasian populationshttp://stores.pkuperspectives.com/catalog/PKU2web.jpghttp://tay-sachs-disease.wikispaces.com/file/view/bb_feb2007_large.jpg/34183391/bb_feb2007_large.jpghttp://www.medicalook.com/diseases_images/cystic_fibrosis.jpg

AUTOSOMAL DOMINANT(Homozygous Dominant = LETHAL)

ACHONDROPLASIA“Dwarfism”Growth plates in long bones fuse too early

HUNTINGTON’S Multiple CAG repeats result in neurological degeneration in middle age

Hear song

AUTOSOMAL CODOMINANTSICKLE CELL ANEMIAMutation in hemoglobin geneCauses red blood cells to change shape in low oxygen conditionsMore common in African Americans

HETEROZYGOTE ADVANTAGE:1 sickle cell allele/1 normal allele provides protection against MALARIA

Watch a video about sickle cell and malaria

DOMINANCE ?

CODOMINANCE? INCOMPLETE DOMINANCE ?

Depends on how you look at it!

CLOSER LOOK AT RELATIONSHIP BETWEEN DOMINANCE AND PHENOTYPEREVEALS AN INTRIGUING FACT:

TAY-SACHS DISEASE Human genetic disorder in which brain cells are

unable to metabolize certain lipids because

a crucial enzyme does not work properly.

As these lipids build up in brain infant suffers seizures, blindness, loss of motor & mental function > > > leads to early death.

At ORGANISMAL LEVEL acts as a recessive trait.Child with two copies of Tay-Sachs allele (tt-homozygous) has the disorder. Child with Tt or TT does not (COMPLETE DOMINANCE)

At BIOCHEMICAL LEVEL- Tt individual has enzyme activity level in between the TT and tt person (INCOMPLETE DOMINANCE ?)

At the MOLECULAR LEVEL – Tt individual makes equal number of normal and dysfunctional enzyme molecules (CODOMINANT ?)

Image from: http://www.djsfoundation.org/images/Steeler%20pics%20Dylan.jpg

A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division.

• This chromosome will be missing certain genes.

• A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid.

Images from: Biology; Campbell and Reese; Pearson Education, Inc., publishing as Benjamin Cummings

Slide from: Slide show by Dr. Chuck Downing

Alterations of Chromosome Structure

Normal chromosome 9Reciprocal

translocation

Translocated chromosome 9

Philadelphiachromosome

Normal chromosome 22 Translocated chromosome 22

Chromosomal translocations between nonhomologous chromosome are also associated with human disorders.

Chromosomal translocations have been implicated in certain cancers, including chronic myelogenous leukemia (CML).

CML occurs when a fragment of chromosome 22 switches places with a small fragment from the tip of chromosome 9.

http://www.antigenics.com/diseases/images/philly_chrom.gif


• An inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation.

• In translocation, a chromosomal fragment joins a nonhomologous chromosome.

Slide from: Slide show by Dr. Chuck DowningImages from: Biology; Campbell and Reese; Pearson Education, Inc., publishing as Benjamin Cummings

See a Video

See a Video


Cri du chatIs a disorder caused by a deletion in chromosome #5

•Mental retardation•Small head•Unusual facial features• “cat cry”

http://www.morfosa.org/medweb/patologi/bilder/cri-du-chat.gif

Duplications and translocations are typically harmful

Normal Meiosis Nondisjunction

http://www.tokyo-med.ac.jp/genet/anm/domov.gifhttp://web.udl.es/usuaris/e4650869/docencia/gen_etica/meioferti2.html

Enduring understanding 3.C: The processing of genetic information is imperfect and is a source of genetic variation. Essential knowledge 3.C.1: Changes in genotype can result in changes in phenotype.

c. Errors in mitosis or meiosis can result in changes in phenotype. Evidence of student learning is a demonstrated understanding of each of the following: 2. Changes in chromosome number often result in human disorders with developmental limitations, including Trisomy 21 (Down syndrome) and XO (Turner syndrome). [See also 3.A.2, 3.A.3]

Nondisjunction –Failure of homologous chromosomes OR chromatids to separate at anaphase

NondisjunctionResults in ANEUPLOIDY =one or more chromosomes have extra or missing copies

AFTER FERTILIZATION:Cell with only 1 copy of a chromosome instead of 2

= MONOSOMY

Cell with 3 copies of achromosome instead of 2

= TRISOMY

Most common chromosomal abnormality (1 in 800 births)

Similar facial featuresSlanted eyes / Protruding tongueMild to severe mental retardation50% have heart defects that need surgery to repair

Down syndrome (Trisomy 21)

http://www.healthofchildren.com/images/gech_0001_0002_0_img0096.jpg

Both older (35+ years) and younger (under 16 years) mothers are more at risk.

http://www.hadsa.org/

Some individuals with Down syndrome have the normal number of chromosomes but have all or part of a third chromosome 21 attached to another chromosome by translocation.

http://content.answers.com/main/content/wp/en/thumb/f/f5/180px-Down_syndrome_translocation.png

http://medgen.genetics.utah.edu/photographs/diseases/high/611.gif

Turner syndrome (X0)1 in 5000 births

Females have only one X chromosomeSmall sizeBroad chestSlightly decreased intelligence35% have heart abnormalitiesHearing loss commonReproductive organs don’t develop at puberty

1 in 2000 births live births

Males have extra X chromosomes (Can be XXy, XXXy, or XXXXy)

Taller than averageNormal intelligencehave male sex organs, but are sterile.may be feminine characteristics,

Often not discovered until puberty when don’t mature like peers

Presence of BARR BODIES

Klinefelter syndromehttp://www.akdeniz.edu.tr/tip/histoloji/embrders_dosyalar/slide0228_image1186.jpg

Image from Biology; Campbell and Reece; Pearson Prentice Hall publishing as Benjamin Cummings © 2006

Karyotype can show:• Sex of baby

• Missing or extra chromosomes

• Major deletions or translocations

• Can’t see individual gene changes

http://content.answers.com/main/content/wp/en/thumb/f/f3/220px-Down_syndrome_translocation.png

Polyploidy -common among plants

Ex: Strawberries = octaploid wheat = hexaploid

Much less common in animals LETHAL in humans

Polyploids are more nearly normal in phenotype than aneuploids.

http://tasty-dishes.com/data_images/encyclopedia/strawberry/strawberry-03.jpgCopyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Enduring understanding 3.C: The processing of genetic information is imperfect and is a source of genetic variation. Essential knowledge 3.C.1: Changes in genotype can result in changes in phenotype. c. Errors in mitosis or meiosis can result in changes in phenotype. Evidence of student learning is a demonstrated understanding of each of the following: 1. Changes in chromosome number often result in new phenotypes, including sterility caused by triploidy and increased vigor of other polyploids. [See also 3.A.2]

POLYPLOIDY Organisms with more than two complete sets of chromosomes

Can occur when a normal gamete fertilizes another gamete in which there has been nondisjunction of all its chromosomes.

Results in triploid (3n) zygote

OR if 2n zygote fails to divide after replicating its chromosomes Results in a tetraploid (4n) embryo


If having extra chromosomes causes genetic problems, how come having two X chromosomes in females and one X in males is not a problem?

X-chromosome Inactivation

http://fig.cox.miami.edu/~cmallery/150/gene/barr.htm

In female cells ONE X chromosome is randomly switched off

It condenses and forms a dense region in the nucleus called a BARR BODY

FEMALE CATS:Female cat can have BOTH black and orange spots

http://www.islandstrolling.com/mainland/peloponnes/photo/mystra_cat_white_orange_black.jpg

In cats the gene thatcontrols color is carried on the X chromosome

Tortoiseshell cats express different alleles in different cells

CAT COLORhttp://www.eagle.ca/~roda/RodMerArts/SwallowHill/Kiisu.html

See a video

MALE cats have only one X chromosome, so they can only have ONE COLOR of spots!

http://ascensionparish.net/forum/messages/14/2493.jpg

THINK ABOUT IT?How many colors of spots could a male cat withKlinefelter syndrome have?

CAT COLOR

“La Monstrua Vestida” “La Monstrua Desnuda”

Paintings in Prado Museum in Madrid by Juan Carrneño Miranda

of a 5 year old girl named Eugenia Marinez Vallejo

Images from: http://www.fisterra.com/human/3arte/pintura/temas/enanos/enanos.asp

PRADER-WILLI Syndrome

Victor Age 1 Victor Age 2

Born floppy and paleAt first refuse to nurse, but later eat until they become obeseTiny hands and feetUnderdeveloped sex organsMildly retardedSpectacular temper tantrums especially if refused foodExceptional proficiency with Jig-saw puzzlesMissing piece of chromosome #15

ANGELMAN’S SYNDROME

http://www.usmagazine.com/colin_farrell_and_son

Colin Farrell’s son has Angelman’s syndrome

Taut, not floppyThinHyperactiveInsomniacSmall headMove jerkily like puppetsHappy dispositionSeverely mentally retarded

Rarer than Prader-WilliMissing SAME piece of Chromosome #15

WHAT’S THE DIFFERENCE?

• In Prader-Willi missing piece of #15 was from father

• In Angelman’s, missing piece of #15 was from the mother

How does a gene “remember” where it came from?GENOMIC IMPRINTING

EPIGENETICS “above genetics”

Molecules sit on top of the genome

Control which genes are ON or OFF

http://www.teachersdomain.org/assets/wgbh/biot09/biot09_vid_epigenetics/biot09_vid_epigenetics_l.jpg

GENOMIC IMPRINTINGInvolves the silencing of certain genes that are “stamped” with an imprint during gamete production so same allele (maternal or paternal) is expressed in all body cells

• Involves methylation (-CH3) (turns genes OFF)or demethylation (turns genes on)

of cytosine nucleotides

http://www.scq.ubc.ca/wp-content/uploads/2006/08/methylation%5B1%5D-GIF.gif

Several hundred mammalian genes, many critical for development, may be subject to imprinting.

• In the new generation, both maternal and paternal imprints are apparently “erased” in gamete-producing cells.

• Then, all chromosomes are reimprinted according to the sex of the individual in which they reside.

• Imprinting is critical for normal development.


Addition or removal or “methyl tags” may beinfluenced by environment

•Twins start with same methyl tags but become more different with age

•Agouti rats – changing diet of pregnant mom can change expression of genes

http://www.precisionnutrition.com/wordpress/wp-content/uploads/2009/12/Figure-3-Agouti-mice.jpg

VIDEO

Addition or removal or “methyl tags” may beinfluenced by environment

•DIET•STRESS•EXERCISE•CHEMICALS

http://www.naturepedic.com/blog/wp-content/uploads/2010/11/BPA_free_logo.jpghttp://www.knowabouthealth.com/wp-content/uploads/2010/06/mcdonalds_.jpghttp://emilyscarenhealth.wordpress.com/2011/10/04/attention-a-must-read-for-smokers/

GENOMICIMPRINTING

• Tags Maternal/Paternal chromosomes

• Differentiation of cell types (blood, skin, etc)

• Embryonic development

• Changes in puberty, pregnancy, aging

• X chromosome inactivation (Barr bodies)

• differences can lead to diseases (cancer)

and genetic disordershttp://www.molekularbiologie.abi.med.uni-muenchen.de/ueber_uns/schotta/index.html

LINKS TO CANCER

http://www.landesbioscience.com/journals/epigenetics/

BRCA = tumor suppressor gene

If it’s turned OFFcancer cells are NOT repaired and can growinto a tumor

Fragile X syndrome, which leads to various degrees of mental retardation, also appears to be subject to genomic imprinting.

• This disorder is named for an abnormal X chromosome in which the tip hangs on by a thin thread of DNA.

• This disorder affects one in every 1,500 males and one in every 2,500 females.

• Inheritance of fragile X is complex, but the syndrome is more common when the abnormal chromosome is inherited from the mother.

• This is consistent with the higher frequency in males.

• Imprinting by the mother somehow causes it.

Slide Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Image from: http://www.lakeforest.edu/images/userImages/eukaryon/Page_6605/Fig-1.jpg

SO WHAT?

•It’s not just a MOM thing•Epigenetic therapy in future ????•How does what you do affect your kids’ and grandkids’ epigenome?

http://www.naturepedic.com/blog/wp-content/uploads/2010/11/BPA_free_logo.jpghttp://www.knowabouthealth.com/wp-content/uploads/2010/06/mcdonalds_.jpghttp://emilyscarenhealth.wordpress.com/2011/10/04/attention-a-must-read-for-smokers/

We are just beginning to understand . . .

c. Some traits result from nonnuclear inheritance. Evidence of student learning is a demonstrated understanding of each of the following: 1. Chloroplasts and mitochondria are randomly assorted to gametes and daughter cells; thus, traits determined by chloroplast and mitochondrial DNA do not follow simple Mendelian rules.

2. In animals, mitochondrial DNA is transmitted by the egg and not by sperm; as such, mitochondrial-determined traits

are maternally inherited.

http://faculty.clintoncc.suny.edu/faculty/michael.gregory/files/Bio%20100/Bio%20100%20Lectures/meiosis/img025.gif

EXTRANUCLEAR GENESThe inheritance of traits controlled by genes present in the chloroplasts or mitochondria

Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg

EX: Variegated leaves result frommutations in pigment genes located inplastids inherited from mother

Image from Biology; Campbell and Reece; Pearson Prentice Hall publishing as Benjamin Cummings © 2005

EXTRANUCLEAR GENES

http://www.ncl.ac.uk/nnp/research/mrg/advice/inheritance.htm

Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATP

MITOCHONDRIAL DISEASES are RARE

Accumulation of mitochondrial mutations may play role in aging process, diabetes, heart disease, Alzheimer’s

•EX: mitochondrial myopathy-• weakness, • intolerance of exercise• muscle deterioration

http://employees.csbsju.edu/hjakubowski/classes/ch331/oxphos/mitochondria.gif

Essential knowledge 3.A.3:d. Many ethical, social and medical issues surround human genetic disorders.

To foster student understanding of this concept, instructors can choose an illustrative example such as: • Reproduction issues • Civic issues such as ownership of genetic information, privacy, historical contexts, etc.

http://media2.abc2news.com//photo/2012/11/22/DNA_Supreme_ourt_109850000_20121122000601_320_240.JPGhttp://www.genewatch.org/uploads/865d357353e86dfc74ba59e18bffed98/GenTesting.gifhttp://www.rainydaybooks.com/files/rainyday/files/RebeccaSkloot.jpg

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Http:// AP BIOLOGY Chapter 15 Chromosomal Basis of Inheritance Big Idea 3: Living systems