Introduction to Human Genetics But what happens when meiosis goes wrong? What when wrong? Happens...

Introduction to Human Genetics

But what happens when meiosis goes wrong?

What when wrong?Happens meiosis wrong?

When wrong?What meiosis goes wrong? Boehm

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Goals of Meiosis• What do you think they are?

Normal MeiosisStarting cell chromosomes

Phase showing chromosomes in Meiosis I

End of Meiosis I

End of Meiosis II

Phase showing chromosomes in Meiosis II

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Meiosis leads to genetic variability• The three sources of genetic variability in a sexually

reproducing organism are:– Independent assortment of homologous chromosomes and

sister chromatids (Punnett square).– Crossing over.– Random fertilization of an ovum by a sperm.

• All three mechanisms reshuffle the various genes carried by individual members of a population.

• BUT mutations are what ultimately create a population’s diversity of genes• some mutations can be beneficial, while others

can be harmful to an individual.

The process of meiosis isn’t perfect• Human disorders can result from mistakes in

meiosis– These disorders can be caused by:• Chromosomal number abnormalities (too many or too

few chromosomes)• Sections of entire chromosomes can be deleted, added,

or swapped.

• Tests are available to determine in utero if a child has a particular chromosomal disorder.

• One technique, amniocentesis, can be used beginning at the 14th to 16th week of pregnancy.– Fetal cells extracted from amniotic fluid are

cultured and karyotyped to identify some disorders.

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Fig. 14.17aBoehm

Diagnosis of Chromosomal Abnormalities

Example of a Karyotype

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Alterations of chromosome number cause some genetic disorders

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Abnormal Meiosis Resulting in Chromosome Number Issues

Starting cell chromosomes

Phase showing chromosomes in Meiosis I

End of Meiosis I

End of Meiosis II

Phase showing chromosomes in Meiosis II

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• Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter cells.– Homologous

chromosomes do not separateduring meiosis I.

– Alternatively, sister chromatids may fail to separate during meiosis II.

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Fig. 15.11Boehm

Source of Chromosome Number Abnormalities

• Some gametes receive two of the same type of chromosome and another gamete receives no copy.

• Offspring results from fertilization of a normal gamete with one after nondisjunction will have an abnormal chromosome number or aneuploidy.– Trisomic cells = 2n + 1(extra) total chromosomes.– Monosomic cells = 2n - 1(too few) chromosomes.

• If the organism survives, aneuploidy typically leads to a distinct phenotype.

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Consequences of Nondisjunction

• Several serious human disorders are due to alterations of chromosome number and structure.

• Although the frequency of aneuploid zygotes may be quite high in humans, most embryos are spontaneously aborted before birth.

• Certain aneuploid conditions upset the balance less, leading to survival to birth and beyond.

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Consequences of Nondisjunction

• One aneuploid condition, Down syndrome, is due to three copies of chromosome 21.– It affects one in 700 children born in the United States.

• This trisomy severely alters an individual’s phenotype in specific ways.

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin CummingsFig. 15.14 Boehm

Down Syndrome

• Trisomies of other chromosomes also increase in incidence with maternal age, but it is rare for infants with these autosomal trisomies to survive for long.

• Why do you also think survival of a trisomy 21 human is more likely than most other, fatal trisomies?

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Trisomy Frequency

• Nondisjunction of sex chromosomes produces a variety of aneuploid conditions in humans.

• Unlike autosomes, this aneuploidy upsets the genetic balance less severely.– Why do you think this is true?

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Sex Chromosome Aneuploidy

Map of Genes on Human Chromosomes

• Klinefelter’s syndrome, an XXY male, occurs once in every 2000 live births.– These individuals have male sex organs, but are sterile.– There may be feminine characteristics, but their intelligence

is normal.

• Males with an extra Y chromosome (XYY) tend to be somewhat taller than average, and are fertile.

• Trisomy X (XXX), which occurs once in every 2000 live births, produces fertile, healthy females.

• Monosomy X or Turner’s syndrome (X0), which occurs once in every 5000 births, produces phenotypic, but immature, sterile females.

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Sex Chromosome Aneuploidy

Other types of errors in meiosis

Sometimes parts of entire chromosomes are deleted, added, or

moved.

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• A deletion occurs when a chromosome fragment lacking 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.

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Fig. 15.13a & b

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Chromosome Structure Abnormalities

• 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

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin CummingsFig. 15.13c & d Boehm

Chromosome Structure Abnormalities

• Deletions and duplications are common in meiosis.–Homologous chromatids may break and rejoin

at incorrect places, such that one chromatid will loose more genes than it receives.

• When do you think these errors could occur in the overall process of meiosis?

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Chromosome Structure Abnormalities

• Deletions cause severe physical and mental problems.

• One syndrome, cri du chat, results from a specific deletion in chromosome 5.– These individuals are mentally retarded, have a

small head with unusual facial features, and a cry like the mewing of a distressed cat.

– This syndrome is fatal in infancy or early childhood.

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

Chromosome Structure Abnormality:Deletion

• Chromosomal translocations can occur between nonhomologous chromosomes.

• 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 (commonly referred to as the “Philadelphia chromosome”).

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Chromosome Structure Abnormality:Translocation

Now can you go diagnose a patient?

• Well, we wouldn’t really trust you to do that after just this one presentation, but…

• Use the class handout of three karyotypes to diagnose the patients as “normal” or “abnormal” in terms of chromosome structure and number.