Results of Abnormal Results of Abnormal MeiosisMeiosis

Biology 30Biology 30

TMSSTMSS

Mrs. S. Pipke-PainchaudMrs. S. Pipke-Painchaud

DefinitionsDefinitions

Karyotype:Karyotype:– a method used to organize the a method used to organize the

chromosomes of a cell in relation to chromosomes of a cell in relation to number, size and type.number, size and type.

– Human Human KaryotypeKaryotype: : http://www.people.virginia.edu/~rjh9u/karyotyp.htmlhttp://www.people.virginia.edu/~rjh9u/karyotyp.html

– The Biology Project - The Biology Project - KaryotypingKaryotyping activity: activity: http://www.biology.arizona.edu/human_bio/activities/karyotypinhttp://www.biology.arizona.edu/human_bio/activities/karyotyping/karyotyping.htmlg/karyotyping.html

– Google Image Search: Google Image Search: http://http://images.google.ca/images?qimages.google.ca/images?q==karyotype&hlkaryotype&hl=en=en

Chromosomal Chromosomal MutationsMutations

““changes in genetic material that changes in genetic material that involve entire chromosomes or involve entire chromosomes or pieces of them” (Addison Wesley pieces of them” (Addison Wesley 157)157)

Types of MutationsTypes of Mutations: (structural): (structural)– DELETIONDELETION: one or more genes is lost : one or more genes is lost

from the chromosomefrom the chromosome ABCDE --> ABDEABCDE --> ABDE

DUPLICATIONDUPLICATION: during meiosis an : during meiosis an unequal crossover occurs and it unequal crossover occurs and it receives an extra copy from its partner receives an extra copy from its partner chromosome.chromosome.– ABCDE --> ABBCDEABCDE --> ABBCDE

TRANSLOCATIONTRANSLOCATION: a whole or an : a whole or an entire piece of a chromosome entire piece of a chromosome attaches to a different pair.attaches to a different pair.– ABCDE --> ABCABCDE --> ABCXYZXYZDEDE

INVERSIONINVERSION: a piece of a : a piece of a chromosome breaks free, turns chromosome breaks free, turns around and reattaches itself.around and reattaches itself.– ABCDEFGHI--> ABCDABCDEFGHI--> ABCDIHGFEIHGFE

Changing Chromosome Changing Chromosome NumberNumber

Nondisjunction: “failure of chromatids Nondisjunction: “failure of chromatids or chromosomes to separate during or chromosomes to separate during cell division” (Addison Wesley 158).cell division” (Addison Wesley 158).

Nondisjunction: “failure of Nondisjunction: “failure of chromatids or chromosomes to chromatids or chromosomes to separate during cell division” separate during cell division” (Addison Wesley 158).(Addison Wesley 158). What happens when this occurs in What happens when this occurs in Mitosis? Or Meiosis?Mitosis? Or Meiosis?

Mitosis: cell dies, but the organism is not harmed

Meiosis: production of an abnormal gamete; you are dealing with the production of sex cells and the possible creation of a new individual.

Abnormal MeiosisAbnormal Meiosis

NondisjunctionNondisjunction - mistakes sometimes - mistakes sometimes occur during meiosis. This occurs when occur during meiosis. This occurs when 2 homologous chromosomes move to 2 homologous chromosomes move to the same pole during anaphase I. The the same pole during anaphase I. The resulting daughter cells either have one resulting daughter cells either have one too many chromosomes or one less too many chromosomes or one less chromosome.chromosome.

Resulting Human Gametes: have 22 or 24 chromosomes. If fertilized by a normal cell they have 45 and 47 chromosomes.

When an abnormal gamete joins with When an abnormal gamete joins with

a normal gamete . .a normal gamete . . . .

Monosomy: “zygote receives only Monosomy: “zygote receives only one of a particular type of one of a particular type of chromosome instead of two, as a chromosome instead of two, as a normal gamete would” (Addision normal gamete would” (Addision Wesley 158).Wesley 158).– The zygote has 45 chromosomes. The zygote has 45 chromosomes. – One less. (One less. (one homologous one homologous

chromosome is missing its partner)chromosome is missing its partner)

Trisomy: “the zygote receives three Trisomy: “the zygote receives three chromosomes of a particular type chromosomes of a particular type instead of two” (Addision Wesley 158).instead of two” (Addision Wesley 158).– Zygote has 47 chromosomesZygote has 47 chromosomes– One extraOne extra

Once these cells undergo mitosis, every Once these cells undergo mitosis, every cell there after will have an abnormal cell there after will have an abnormal number of chromosomes.number of chromosomes.

In Humans:In Humans: Monosomies and trisomies that occur in Monosomies and trisomies that occur in

embryos are lethal.embryos are lethal.– Down Syndrome (47, 21+) is an exceptionDown Syndrome (47, 21+) is an exception

autosomal trisomy (trisomy 21)autosomal trisomy (trisomy 21) mild to severely disabledmild to severely disabled almond shaped eyesalmond shaped eyes enlarged tonguesenlarged tongues short stocky bodiesshort stocky bodies poor muscle development and coordinationpoor muscle development and coordination possible heart defectspossible heart defects can lead active, productive lives.can lead active, productive lives.

(A.W. 208)

Down SyndromeDown Syndrome

Frequency of Down Syndrome births Frequency of Down Syndrome births increase dramatically with the age of increase dramatically with the age of the mother.the mother.– Age 30 = 1/1000Age 30 = 1/1000– Age 40 = 1/100Age 40 = 1/100

Why?Why? History of Down Syndrome: History of Down Syndrome: TrisomyTrisomy

21 - the story of Down Syndrome 21 - the story of Down Syndrome– http://www.ds-health.com/trisomy.htmhttp://www.ds-health.com/trisomy.htm

RELATIONSHIP OF DOWN SYNDROME INCIDENCE TO MOTHERS' AGE

Mothers Age Incidence of Down Syndrome

Under 30 Less than 1 in 1,000

30 1 in 900

35 1 in 400

36 1 in 300

37 1 in 230

38 1 in 180

39 1 in 135

40 1 in 105

42 1 in 60

44 1 in 35

46 1 in 20

48 1 in 16

49 1 in 12

Source: Hook, E.G., Lindsjo, A. Down Syndrome in Live Births by Single Year Maternal Age.

Info from:

National Institute of Child Health and Human Developmenthttp://www.nichd.nih.gov/publications/pubs/downsyndrome/down.htm

Cause: Random error at the 21st Cause: Random error at the 21st chromosome.chromosome.

Cannot be inheritiedCannot be inheritied

Familial Down Syndrome - 1 arm of the Familial Down Syndrome - 1 arm of the 21st chromosome is copied to one of 21st chromosome is copied to one of the 21st pairs of chromosomes the 21st pairs of chromosomes (translocation). This type can be (translocation). This type can be inheritied.inheritied.

Other Autosomal Other Autosomal TrisomiesTrisomies

Patau Syndrome (47, 13+):Patau Syndrome (47, 13+):– 1-2 per 10 0001-2 per 10 000– extra copy of the 13th chromosomeextra copy of the 13th chromosome– average survival 2.5 daysaverage survival 2.5 days– brain malformations, mentally challenged and heart problemsbrain malformations, mentally challenged and heart problems– The fetus.net The fetus.net http://http://www.thefetus.net/page.php?idwww.thefetus.net/page.php?id=1473=1473

Edwards Syndrome (47, 18+):Edwards Syndrome (47, 18+):– 1 in every 6000-8000 live births1 in every 6000-8000 live births– severely affects internal organsseverely affects internal organs– less than 5% survive >1yearless than 5% survive >1year– found more often in femalesfound more often in females– e-medicine: e-medicine: http://www.emedicine.com/ped/topic652.htmhttp://www.emedicine.com/ped/topic652.htm

PolyploidyPolyploidy

““nondisjunction occurs in all the nondisjunction occurs in all the pairs of chromosomes at once. A pairs of chromosomes at once. A polyploidy organism has three or polyploidy organism has three or more entire sets of chromosomes.” more entire sets of chromosomes.” (Addison Wesley 159).(Addison Wesley 159).– In animals, it is lethal.In animals, it is lethal.– In plants, it can produce a stronger and In plants, it can produce a stronger and

more useful plant with larger flowers more useful plant with larger flowers and fruit.and fruit.

Can occur naturally or in a lab setting.Can occur naturally or in a lab setting. Approx. 25-50% of plant species are Approx. 25-50% of plant species are

polyploid. (A.W. 159)polyploid. (A.W. 159)– Triticum aestivumTriticum aestivum - wheat (bread) 42 - wheat (bread) 42

chromosomeschromosomes originated 8000 years agooriginated 8000 years ago a hybrid of ancient wheat (28) and wild grass (14)a hybrid of ancient wheat (28) and wild grass (14) PotatoesPotatoes OatsOats

– ~ Addison Wesley 159~ Addison Wesley 159

Other Examples

Polyploid ExamplesPolyploid Examples Normal = 2n or diploidNormal = 2n or diploid Triploid (3n) - sterileTriploid (3n) - sterile

– potatoes (larger), bananas (soft seeds - wild potatoes (larger), bananas (soft seeds - wild bananas have hard seeds), seedless water bananas have hard seeds), seedless water melonsmelons

Tetraploid (4n) Tetraploid (4n) – alfalfa, coffee, peanuts, Macintosh Apples, alfalfa, coffee, peanuts, Macintosh Apples,

white potato, tobacco, cottonwhite potato, tobacco, cotton Others:Others:

– Octaploid Strawberries, Oats (6n)Octaploid Strawberries, Oats (6n)

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Polyploidy in animalsPolyploidy in animals– although most often fatal examples do although most often fatal examples do

exist in some insects, fish, amphibians exist in some insects, fish, amphibians and reptiles.and reptiles.

– Only one mammalian examples exists: Only one mammalian examples exists: Argentinean Rat (4n = 102)Argentinean Rat (4n = 102)

– http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polyploidy.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polyploidy.html

– some salmon, African Frogs some salmon, African Frogs (MadSci.nethttp://www.madsci.org/posts/archives/Apr2003/1049863034.Cb.r.html(MadSci.nethttp://www.madsci.org/posts/archives/Apr2003/1049863034.Cb.r.html

Nondisjunction of the Nondisjunction of the Sex ChromosomesSex Chromosomes

Turner’s Syndrome (45, X):Turner’s Syndrome (45, X):– monosomymonosomy– born female, short, webbed neck, broad born female, short, webbed neck, broad

shield like chestshield like chest– 1 in 3000 female births1 in 3000 female births

normal in childhood, normal intelligence. normal in childhood, normal intelligence. Adolescence: never reach normal height, do not Adolescence: never reach normal height, do not

develop sexually and are sterile. (A.W. 209)develop sexually and are sterile. (A.W. 209)– Turner Syndrome Society: Turner Syndrome Society:

http://www.turner-syndrome-us.org/resource/faq.htmlhttp://www.turner-syndrome-us.org/resource/faq.html

Klinefelter Syndrome (47, Klinefelter Syndrome (47, xxy)xxy)

Trisomy; 1 in 700Trisomy; 1 in 700 tall, male, steriletall, male, sterile underdeveloped testes, can cause some underdeveloped testes, can cause some

feminine features (I.e. body shape, breast feminine features (I.e. body shape, breast development) (A.W. 208)development) (A.W. 208)

can also karyotype 48 XXXY; 48XXYY; 49 XXXXYcan also karyotype 48 XXXY; 48XXYY; 49 XXXXY– y chromosome determines maleness; absence of y = y chromosome determines maleness; absence of y =

female (Turner’s Syndrome)female (Turner’s Syndrome)– may be some developmental delays (especially in the area of language) (National may be some developmental delays (especially in the area of language) (National

Institute of Health - Institute of Health - http://www.nichd.nih.gov/publications/pubs/klinefelter.htm#xwhat)http://www.nichd.nih.gov/publications/pubs/klinefelter.htm#xwhat)

Defective Chromosome Defective Chromosome StructureStructure

Cri-du-chat Syndrome: Cri-du-chat Syndrome: – significant deletion from chr 5significant deletion from chr 5– baby’s cry sounds like a cat’s meowbaby’s cry sounds like a cat’s meow– small headssmall heads– severely developmentally disabledseverely developmentally disabled– rarely live past 1 or 2rarely live past 1 or 2– (A.W. 209)(A.W. 209)– 1 in 20 000 to 50 000 births (Genetics 1 in 20 000 to 50 000 births (Genetics

Home Reference: Home Reference: http://ghr.nlm.nih.gov/condition=criduchatsyndrome#definitionhttp://ghr.nlm.nih.gov/condition=criduchatsyndrome#definition

Single Allele DisordersSingle Allele Disorders

Gene Mutations: (point mutations)Gene Mutations: (point mutations)– mutations of a single gene because of mutations of a single gene because of

small errors in the sequence of or small errors in the sequence of or number of nucleotides which cause a number of nucleotides which cause a change in amino acids.change in amino acids.

GGU --> GGUGGU --> GGU CCA --> CAACCA --> CAA

Recessive Genetic Recessive Genetic DisordersDisorders

Tay Sachs Disease:Tay Sachs Disease:– fatal; inability to break down a lipid; fatal; inability to break down a lipid;

causes an accumulation in the brain = causes an accumulation in the brain = blindness, then seizuresblindness, then seizures

– death occurs within the first year of lifedeath occurs within the first year of life– higher rate in Ashkenzai Jews (Central higher rate in Ashkenzai Jews (Central

Europe)Europe)– (A.W. 210)(A.W. 210)

Cystic fibrosis:Cystic fibrosis:– mutation that causes an excessive mutation that causes an excessive

amount of mucous to be released by the amount of mucous to be released by the pancreas, lungs and other organs.pancreas, lungs and other organs.

– Leads to blocked digestive tract, Leads to blocked digestive tract, congested lungs and other pnemonia like congested lungs and other pnemonia like infectionsinfections

– No treatment = death at early ageNo treatment = death at early age– Treatment can prolong life until adulthoodTreatment can prolong life until adulthood

Dominant Allele DisordersDominant Allele Disorders

Are less common . . . Why?Are less common . . . Why?– Because individuals die before reproducingBecause individuals die before reproducing

Huntington’s Disease:Huntington’s Disease:– fatal disorders that results in deterioration of the brain and nervous systemfatal disorders that results in deterioration of the brain and nervous system– symptoms appear in later 30s and early symptoms appear in later 30s and early 40s40s– already passed gene onto childrenalready passed gene onto children– (A.W. 211) Other Dominant Alleles(A.W. 211) Other Dominant Alleles

Codominant DisordersCodominant Disorders Sickle Cell DiseaseSickle Cell Disease

– Hemoglobin A = NormalHemoglobin A = Normal– Hemoglobin S = Sickle CellHemoglobin S = Sickle Cell– both are codominantboth are codominant

an attack begins with a lack of oxygen, HemS cells an attack begins with a lack of oxygen, HemS cells form long chains. The RBC become sickle shaped form long chains. The RBC become sickle shaped and tangle. The clumped cells will clog capillaries and tangle. The clumped cells will clog capillaries and stop blood flow. Sickling crisis is very painful and stop blood flow. Sickling crisis is very painful and may cause death.and may cause death.

High incidence in Africa and the Middle East because High incidence in Africa and the Middle East because being heterozygous offers some resistance to being heterozygous offers some resistance to malaria. (A.W. 211-212)malaria. (A.W. 211-212)

Is it possible to have anIs it possible to have anXY female or an XX male?XY female or an XX male?

YesYes– on the Y chromosome there is an SRY on the Y chromosome there is an SRY

Region (Sex Determining Region), Region (Sex Determining Region), which is responsible for male which is responsible for male development. If this regions gets development. If this regions gets translocated to an X it will cause translocated to an X it will cause Maleness.Maleness.

XY Female - SRY region is missingXY Female - SRY region is missing XX Male - SRY region translocated to XXX Male - SRY region translocated to X

Autosomal vs Sex Chromosome Autosomal vs Sex Chromosome TrisomiesTrisomies

In 1961, Mary Lyon proposed that In 1961, Mary Lyon proposed that early on in development of a normal early on in development of a normal female, one X chromosome in each female, one X chromosome in each body cell is inactivated.body cell is inactivated.

She suggested the inactive X She suggested the inactive X chromosome was the darkly staining chromosome was the darkly staining mass, called a Barr Body that mass, called a Barr Body that normally appears in the nuclei of normally appears in the nuclei of female cells.female cells.

– Thus, one reason sex chromosomes Thus, one reason sex chromosomes trisomies are less disruptive is because trisomies are less disruptive is because all of the extra X chromosomes are all of the extra X chromosomes are inactivated except for a few active genes.inactivated except for a few active genes.

Example: Calico and Tortoise Shell cats are Example: Calico and Tortoise Shell cats are always female. WHY?always female. WHY?

- Heterozygous - X inactivation is random

- one X (Orange) one X (Black); where ever an orange X is inactivated the black will show. If the Black X is inactivated the orange color will show. When the cells go through mitosis and grow, the cat develops patches of black fur and patches of orange fur.

Examples of Dominant Examples of Dominant AllelesAlleles

DimplesDimples frecklesfreckles widow’s peakwidow’s peak farsightednessfarsightedness broad lipsbroad lips polydactyly (extra digits)polydactyly (extra digits)

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Why does it increase with Why does it increase with the mother’s age?the mother’s age?

– All primary oocytes are formed by All primary oocytes are formed by birthbirth

– once ovulation begins each once ovulation begins each succeeding oocyte has been stopped succeeding oocyte has been stopped in meiosis for a progressively longer in meiosis for a progressively longer period of timeperiod of time

– older primary oocyte means a greater older primary oocyte means a greater chance of deterioration or exposure chance of deterioration or exposure to other harmful elements.to other harmful elements.

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Other Genetic DisordersOther Genetic Disorders

Color Blindness (Sex Linked)Color Blindness (Sex Linked) Muscular DystrophyMuscular Dystrophy Hemophilia (Sex Linked)Hemophilia (Sex Linked)