Transcript View Ch. 13 PowerPoint here.

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
– 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
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• 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
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• Morgan crossed F1 females x F1 males
• F2 generation contained red and whiteeyed 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
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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
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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.
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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
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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
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• 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.
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• 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.
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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
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• Smallest autosomes can present as 3
copies and allow individual to survive
– 13, 15, 18, 21 and 22
– 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
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Down syndrome
•
•
•
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Women 20-30 – 1 in 1,400 births.
Women 30-35 - 1 in 750 births.
By age 35 – 1 in 400
Over 45 – 1 in 35
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• 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.
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• 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.
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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
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• 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.
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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
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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.
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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.
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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
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Mitochondria have their own genomes.
• Passed to offspring in the egg and leads to
maternal inheritance.
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