Chromosomes, Mapping, and the Meiosis–Inheritance Connection Chapter 13

Learning outcomes What is the evidence for genes being on chromosomes? Explain how mutations can cause disease. What are the consequences of nondisjunction in humans?

Carl Correns – 1900 Walter Sutton – 1902 First suggests central role for chromosomes One of papers announcing rediscovery of Mendel’s work Walter Sutton – 1902 Chromosomal theory of inheritance Based on observations that similar chromosomes paired with one another during meiosis

T.H. Morgan – 1910 Working with fruit fly, Drosophila melanogaster Discovered a mutant male fly with white eyes instead of red Crossed the mutant male to a normal red-eyed female All F1 progeny red eyed = dominant trait

Morgan crossed F1 females x F1 males F2 generation contained red and white- eyed flies But all white-eyed flies were male Testcross of a F1 female with a white-eyed male showed the viability of white-eyed females Morgan concluded that the eye color gene resides on the X chromosome

Sex Chromosomes Sex determination in humans is based on the presence of a Y chromosome 2 X chromosomes = female Having a Y chromosome (XY) = male

© BioPhoto Associates/Photo Researchers, Inc. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. X chromosome Y chromosome 2.8 µm © BioPhoto Associates/Photo Researchers, Inc. Humans have 46 total chromosomes 22 pairs are autosomes 1 pair of sex chromosomes Y chromosome highly condensed Recessive alleles on male’s X have no active counterpart on Y “Default” for humans is female Requires SRY gene on Y for “maleness” - masculinization of genitalia and secondary sex organs.

Hemophilia Human genetic disorders show sex linkage when the relevant gene is on the X chromosome. An example is hemophilia - Disease that affects a single protein in a cascade of proteins involved in the formation of blood clots Form of hemophilia is caused by an X-linked recessive allele Heterozygous females are asymptomatic carriers Allele for hemophilia was introduced into a number of different European royal families by Queen Victoria of England

Dosage compensation Prevents doubling of sex-linked gene products. Ensures an equal expression of genes from the sex chromosomes even though females have 2 X chromosomes and males have only 1 In each female cell, 1 X chromosome is randomly inactivated and is highly condensed into a Barr body

Females heterozygous for genes on the X chromosome are genetic mosaics Allele for black coat is on one X, the allele for orange is on the other. Black appears when allele for orange is inactivated, and vice versa.

Calico cats are almost always female because the X chromosome determines the color of the cat and a female cat has two X chromosomes. A common male cat has one X and one Y chromosome. Since the Y chromosome does not have any color genes, there is no chance he could have both orange and non-orange together. One main exception to this is when, in rare cases, a male has XXY chromosomes, in which case the male could have tortoiseshell or calico markings. Most male calico or tortoiseshell cats are sterile due to the abnormality of carrying two X chromosomes.

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Genetic Mapping Early geneticists realized that they could obtain information about the distance between genes on a chromosome Based on genetic recombination (crossing over) between genes If crossover occurs, parental alleles are recombined producing recombinant gametes Genes close together on a single chromosome are said to be linked. As physical distance on a chromosome increases, so does the probability of recombination (crossover). This allows genetic maps to be constructed based on the frequency of recombination.

Nondisjunction Failure of homologues or sister chromatids to separate properly during meiosis Aneuploidy – gain or loss of a chromosome Monosomy – loss Trisomy – gain In all but a few cases, do not survive

Smallest autosomes can present as 3 copies and allow individual to survive 13, 15, 18 – severe defects, die within a few months 21 and 22 – can survive to adulthood Down Syndrome – trisomy 21 May be a full, third 21st chromosome May be a translocation of a part of chromosome 21 Mother’s age influences risk

Down syndrome Women 20-30 – 1 in 1,400 births. By age 35 – 1 in 400 Over 45 – 1 in 35

Trisomy 13 (Patau Syndrome) The incidence of Trisomy 13 is is approximately 1 out of 16,000 live births. Trisomy 13 produces intellectual and physical handicaps, skull and facial abnormalities, and defects in all organ systems. It is also associated with a left lip, a large, triangular nose, and extra digits. Eighty percent die in the first month, five to ten percent live past the first year.

Cri du Chat Syndrome Cri du chat syndrome is due to a deletion of a portion of chromosome 5. Cri du chat individuals are intellectually handicapped. "Cri du chat" is French for "cry of the cat". The infants cry sounds like a cat.

Nondisjunction of sex chromosomes Do not generally experience severe developmental abnormalities Individuals have somewhat abnormal features, but often reach maturity and in some cases may be fertile

XXX – triple-X females – mild symptoms – may have learning disabilities. XXY – males (Klinefelter syndrome) – males, hypogonadism, usually infertile XO – females (Turner syndrome) – short height, broad chest, webbed neck, usually infertile OY – nonviable zygotes XYY – males (Jacob syndrome) – tall, thin males, may have social and learning disabilities.

Detection Pedigree analysis used to determine the probability of genetic disorders in the offspring. Amniocentesis collects fetal cells from the amniotic fluid for examination. Usually needle and fetus are observed with ultrasound. Chorionic villi sampling collects cells from the placenta for examination

Amniocentesis The fetus is surrounded by a layer of liquid called amniotic fluid. Amniocentesis - a sample of amniotic fluid is removed and cells that it contains are grown on a culture dish. Because these cells are of fetal origin, any chromosomal abnormalities present in the fetus will also be present in the cells. Amniocentesis cannot be done until the 14th to 16th week of pregnancy. Cells must then be cultured on a laboratory culture dish for 2 weeks to obtain sufficient numbers of cells.

Chorionic villi Chorionic villi sampling is a procedure in which a small amount of the placenta is removed. It is normally done during the 10th to 12th week but it can be done as early as the 5th week of pregnancy. Karyotype analysis can be performed on these cells immediately after sampling. 

Two exceptions to Chromosomal Inheritance Genomic Imprinting – the expression of a gene depends on whether it passes through the maternal or paternal germ line. Ex. – Epigenetics Epigenetic changes are inheritable but to not involve a change in the DNA

Mitochondria have their own genomes. Passed to offspring in the egg and leads to maternal inheritance.