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

Goals of Meiosis What do you think they are? Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Normal Meiosis Starting cell chromosomes Phase showing chromosomes in Meiosis I End of Meiosis I Phase showing chromosomes in Meiosis II End of Meiosis II Boehm

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.

Diagnosis of Chromosomal Abnormalities 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. Fig. 14.17a Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Example of a Karyotype Boehm

Alterations of chromosome number cause some genetic disorders Boehm

Abnormal Meiosis Resulting in Chromosome Number Issues Starting cell chromosomes Phase showing chromosomes in Meiosis I End of Meiosis I Phase showing chromosomes in Meiosis II End of Meiosis II Boehm

Source of Chromosome Number Abnormalities Nondisjunction occurs when problems with the meiotic spindle cause errors in daughter cells. Homologous chromosomes do not separate during meiosis I. Alternatively, sister chromatids may fail to separate during meiosis II. Fig. 15.11 Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Consequences of Nondisjunction 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. Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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

Down Syndrome 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. Fig. 15.14 Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Trisomy Frequency 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? http://www.genetics.com.au/images/factsheets/fs29-1.gif Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Sex Chromosome Aneuploidy 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? Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Map of Genes on Human Chromosomes

Sex Chromosome Aneuploidy 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. Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Other types of errors in meiosis Sometimes parts of entire chromosomes are deleted, added, or moved. Boehm

Chromosome Structure Abnormalities 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. Fig. 15.13a & b Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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

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

Chromosome Structure Abnormality: Deletion 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. Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Chromosome Structure Abnormality: Translocation 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”). Boehm Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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.