10/27/19
Lecture 16
Chromosomal Basis of Inheritance
•Don’t forget that you can set up an appointment with
me!
•I will have exams with me on Wednesday.
Today: Chromosomes and Inheritance
• Autosomal recessive and dominant traits/ disorders (Follow Mendelian
genetics)
• Sex-linked traits/ disorders
• Pedigrees
• Aberrations in chromosome number:
– Polyploidy
– Aneuploidy
– Abnormal number of sex chromosomes
• Aberrations in chromosome structure:
– Deletion
– Inversion
– Translocation
– Duplication
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Reminder: Autosome versus sex chromosome
A karyotype shows the 46 chromosomes in a human
_______– in humans, 22
pairs of autosomes, which
are non-sex-determining
chromosomes
______– in humans, x and y
- Females (X, X)
- Males (X, Y)
Reminder: Dominant versus recessive
• ______ – the allele that is expressed in the heterozygous
condition
• _______ – the allele that is not expressed in the heterozygous
condition
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Autosomal recessive disorders
• __________ all males and females
• More likely if mating within a family/close relatives
– Why?
• Both parents must be heterozygous for an autosomal
recessive disorder to manifest
– called ___________ because they have the mutant allele but do not
exhibit the disorder
• There is a _______ chance that offspring with have the
disease
Ex.) Autosomal recessive disorders
• Cystic fibrosis
• Albinism
• Most metabolic diseases (Examples - PKU, Tay-Sachs disease)
– PKU (Phenylketonuria) – mutation usually in the enzyme that breaks
down phenylalanine, results in buildup in the brain which causes
neurological problems
– Tay-Sachs disease – mutation that causes neurodegeneration,
common in Ashkenazi Jewish, Cajun, and French Canadian populations
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Ex.) Autosomal recessive disorder –Sickle cell anemia
• Produce hemoglobin S instead of hemoglobin A in red blood cells
• Hemoglobin S forms crystals that distort the cells, disrupt function
• Note: Both parents must be _______.
• There is a 25% chance that offspring with have the disease
• In sickle cell anemia, it turns out that having
hemoglobin S makes heterozygote more resistant to
malaria = ______________
Question
Cystic fibrosis is an autosomal recessive disorder. When two
parents are heterozygous for the disorder, what is the
probability that they will have 1 child with cystic fibrosis?
A. ¼ or (25%)
B. ½ or (50%)
C. ¾ or (75%)
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Question
Cystic fibrosis is an autosomal recessive disorder. If two parents are
heterozygous for the disorder, and they have three children what is
the probability that all three children will be affected with cystic
fibrosis?
A. 1/4
B. 3/4
C. 1/64
D. 1/12
Question
Cystic fibrosis is an autosomal recessive disorder. If two parents
are heterozygous for the disorder, and they have two children
what is the probability that one of the children will be
affected with cystic fibrosis?
A. 1/16 or (6%)
B. 6/16 (or 37.5%)
C. ½ or (50%)
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Autosomal dominant disorders
• Genetic condition in which a single faulty allele on an autosome causes
damage/ a disorder
• ________________, meaning if you have the allele, you have the
phenotype
• Rare
• Ex.) Huntington’s Disease
– Doesn’t develop until late adulthood
– Usually after child bearing years
– Chances of getting it if one parent affected is 1:2 (50%)
– What about if two parents were affected?
• Ex.) Wardenburg syndrome
– Congenital hearing loss, iris pigmentation abnormalities, skin
hypopigmentation, other features abnormal
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Ex.) Autosomal dominant disorder –Huntington’s Disease
• Causes mental impairment and spastic movements
• Usually diagnosed between 35-44 years of age
• If one parent is affected, chance of passing on the disease is 50%
Ethical dilemmas ???
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Today: Chromosomes and Inheritance
• Autosomal recessive and dominant disorders (Follow Mendelian genetics)
• Sex-linked disorders
• Pedigrees
• Aberrations in chromosome number:
– Polyploidy
– Aneuploidy
– Abnormal number of sex chromosomes
• Aberrations in chromosome structure:
– Deletion
– Inversion
– Translocation
– Duplication
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Reminder: Sex chromosomes determine sex
Ø X and Y are not homologous
chromosomes
Ø But they act as though they were
§ Gametes only carry one of the two
Ø Males are XY, females are XX
Ø X chromosome has 1100 genes;
Y has 78 genes
§ Sex-linked genes
§ Many X-linked genes are
unrelated to sex characteristics
§ Most sex-linked disorders are
X-linked
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Sex-linked disorders
• Sex chromosomes in humans are different (X and Y)
• Y-linked
– Rare, in part because there are few genes on the Y chromosome
• X-linked dominant
– In both sexes
– More common in females, because some disorders are fatal in males
with only one X-chromosome
• X-linked recessive
– In both sexes, but more common in males
– Why? The value of having 2 X chromosomes
– Ex.) Hemophilia, Duchenne Muscular Dystrophy, Red/Green color
blindness
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Ex.) X-linked recessive disorder – Red/green color blindness
• Color blindness – inability to distinguish between colors due to problems
with the protein portion of light-absorbing pigments in the eyes
– Blue pigment – on chromosome 7
– Red and green pigment – on X chromosome
Is it possible for a female to have color-blindness? ____
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Sex-linked disorders Conditions
• X- inactivation or Lyonization
– Placental mammals = random
– Blastula stage, each cell (stem cell) picks
one X chromosome to be active
– Classic Example = Tortoiseshell and Calico
cats
– Can a male tortoiseshell or calico cat
exist? 17
Today: Chromosomes and Inheritance
• Autosomal recessive and dominant disorders (Follow Mendelian genetics)
• Sex-linked disorders
• Pedigrees
• Aberrations in chromosome number:
– Polyploidy
– Aneuploidy
– Abnormal number of sex chromosomes
• Aberrations in chromosome structure:
– Deletion
– Inversion
– Translocation
– Duplication
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Pedigree – a pictoral family history constructed
to track a trait
• Frequently used to track medical conditions in a family
• Parents represented by a horizontal line connecting female
and male
• Vertical line between parents indicates offspring
• ?- indicates that second allele is unknown for an individual
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Pedigree – a pictoral family history constructed
to track a trait
• Question: Can a dominant trait skip a generation?
1. Yes
2. No
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Today: Chromosomes and Inheritance
• Autosomal recessive and dominant disorders (Follow Mendelian genetics)
• Sex-linked disorders
• Pedigrees
• Aberrations in chromosome number:
– Polyploidy
– Aneuploidy
– Abnormal number of sex chromosomes
• Aberrations in chromosome structure:
– Deletion
– Inversion
– Translocation
– Duplication
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Aberrations in chromosome number______
• ________– one or more entire sets of chromosomes has been
added to genome of a diploid organism
– So not 2n but rather 3n or more
– How 3n? 1.)
2.)
– Results in death in humans but common in some plants (40% of all
angiosperms, 70% of grasses) and other animal species
– Useful in horticulture: bananas, grapes, oranges, watermelons that
are 3n do not make seeds and tend to be larger with larger fruit
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Aberrations in chromosome number: ______
• __________– more or fewer chromosomes than normally
present in the species full set (the whole set is not altered)
– Occurs more commonly than polyploidy in humans but usually goes
unrecognized due to miscarriage
– All human aneuploidy results in miscarriage except aneuploidy of sex
chromosomes (X and Y), 13, 18, or 21
– ___________– the main cause
• Failure of homologous chromosomes (during Meiosis I) or sister
chromatids (during meiosis II) to separate during cell division
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Aberrations in chromosome number: aneuploidy
– Most common in humans is Trisomy 21:
• Down syndrome – small heads, below
normal IQ, short stature, reduced lifespan,
lifespan, infertility in males
• 90% nondisjunction in egg, 10%
nondisjunction in sperm
• Maternal age is a factor, possibly due to
delay in meiosis during oogenesis
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Aneuploidy is usually caused by nondisjunction
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Aberrations in chromosome number: aneuploidy
• Aneuploidy – more or fewer chromosomes than normally present in
the species full set (the whole set is not altered)
– Can occur in somatic cells – nondisjunction during mitosis
– observed in cancer cells, thought to lead to cancer development
– Can occur in sex chromosomes:
• Turner syndrome – XO
– Females do not undergo puberty, sterile, immature female
secondary sex characteristics, heart and other defects, normal
intelligence
– No known cases of no X chromosomes suggests …
• Klinefelter syndrome – XXY, XXXY
– Males, small testes, reduced facial hair, some female
characteristics, some developmental delays
• Poly X females – XXX or more
– Triplo-X (XXX) – tall thin, sometimes normal fertility, normal
intelligence
– XXXX, XXXXX – normal female anatomy but below average IQ 26
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10/27/19
Aberrations in chromosome number: polyploidy
versus aneuploidy
• Polyploidy – alters the #
of chromosome sets (all
chromosomes have an
extra copy)
• Aneuploidy – alters the
# of chromosomes
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Today: Chromosomes and Inheritance
• Autosomal recessive and dominant disorders (Follow Mendelian genetics)
• Sex-linked disorders
• Pedigrees
• Aberrations in chromosome number:
– Polyploidy
– Aneuploidy
– Abnormal number of sex chromosomes
• Aberrations in chromosome structure:
– Deletion
– Inversion
– Translocation
– Duplication
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Aberrations in chromosome structure
• ________ – a fragment of a chromosome breaks off and does not rejoin
any other chromosome so genes are missing
– Ex.) Cri-du-chat syndrome – deletion of one arm of chromosome 5
• _______ – chromosomal fragment breaks and rejoins a chromosome in
inverted orientation
– Can result in disruptions of gene regulation
• ________ – non-homologous chromosomes exchange pieces
– Reciprocal – switch OR Nonreciprocal – moves 1 part to another chromosome
• _________ – extra copy of a chromosome fragment means extra amount
of genetic info
– Often from crossing over “gone wrong”
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Chromosomal aberration: Balanced
translocations and infertility
Missing white Missing black
chromosome info chromosome info
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Questions
A female human with 47 chromosomes, including only two X chromosomes has:
A. Sex chromosome aneuploidy
B. Sex chromosome polyploidy
C. Autosomal polyploidy
D. Autosomal aneuploidy
A human embryo with 69 chromosomes would:
A. Be considered polyploid
B. Die in the womb
C. Both A and B
D. Neither A nor B
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