Download Inheritance Patterns & Human Genetics

Inheritance Patterns
&
Human Genetics
Chapter 12 Topics:
12-1 Chromosomes & Inheritance
12-2 Human Genetics
Honors/CPI
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Sex Determination
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Thomas Morgan, Columbia University, first identified
the “X” & “Y” chromosome
He studied the fruit fly, Drosophila, which has 4
homologous pairs of chromosomes
He found that one set of chromosomes in females
looked the same, while in males one was smaller
He surmised (correctly) that these controlled the sex
of the individual
He labeled the female XX & the male XY
During meiosis, the gametes formed contain either
an X or a Y chromosome
Thus the resulting zygote will be XX or XY
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Sex Linkage
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Genes are located on sex chromosomes are sexlinked genes
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Some are X-linked genes
Some are Y-linked genes
In Drosophila, eye color is sex-linked
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Morgan found females had red eyes, but some males had
white eyes.
Why are there no white-eyed females?
Morgan crossed a red-eyed female with a white-eyed male
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Result: F1 100% Red-eyed
Crossed F1
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Result: F2 75% Red-eyed, 25% White-eyed (males)
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Assume:
eye color linked to X chromosome
R – dominant allele (red eye)
r – recessive allele (white eye)
XrY
Male Parent
XRXR
Female
Parent
F1
Xr
XR
XRXr XRY
XR
XRXr XRY
Y
XRY
Male Parent
XRXr
Female
Parent
F2 XR
Y
XR XRXR XRY
Xr XRXr XrY
So, why are there no white-eyed females?
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Linkage Groups
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Chromosomes contain thousands of genes
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Genes located on one chromosome form a linkage group
and tend to be inherited together
In Drosophila, grey body color dominant to black body color
& long wings are dominant to short wings; these form a
linkage group and so they are passed together to gametes
Crossing-over can occur during meiosis I
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Exchange of genes between homologous pairs
So, this disrupts linkage groups and introduces a
rearrangement of the genes in gametes
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Mutation – change in the nucleotide
sequence of DNA
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Germ cell mutations – affect the gametes
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Somatic cell mutations – affect organism’s cells, can
disrupt/affect cellular activities, often resulting in
cancers
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Cannot affect cellular activities of organism
Cannot be passed to offspring
Lethal mutations – result in death, often prior to birth
Some mutations are beneficial enabling organism’s
phenotype to be enhanced in some way
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Mutation Types
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Deletion – a change in chromosome structure or a loss of part of
a chromosome
Inversion – a segment breaks off & reattaches in reverse
orientation
Translocation – a segment breaks off & reattaches to another
chromosome
Nondisjunction – failure of homologues to separate during
meiosis, one gamete gets an extra while other gamete gets none
or some portion of a homologue
Point Mutation – substitution, addition, or removal of a nucleotide
 Substitutions – one nucleotide in a codon is replaced by a
different nucleotide resulting in a new codon; this changes amino
acid for which it codes
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Sickle-Cell Anemia
Substitution Point Mutation
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Adenine is substituted for thymine of 1 codon
DNA  mRNA  Amino Acid
Normal
CTT  GAA  Glutamic Acid
Point Mutation
CAT  GUA  Valine
This amino acid important to formation of hemoglobin molecule
 Heterozygous individuals have one allele with the point mutation;
sickle cell trait
 Homozygous recessive individuals have 2 alleles with the point
mutation; sickle cell anemia
Sickle cell trait results in normal & abnormal RBCs
 In US, 1 in 10 Americans of African descent are carriers
Sickle cell anemia results in abnormal RBCs; causes intense
pain, tissue damage, death
 In US, 1 in 500 Americans of African descent are afflicted
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Pedigrees
“A Family Tree”
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Punnett squares are helpful, but provide only
information on one generation at a time
Pedigree analysis provides a pattern of inheritance
within a family grouping
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Phenotypes of family members are studied
Rules for making a pedigree
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Circles are females; squares are males
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If circle/box is cut in ½ individual is heterozygous
Horizontal lines represent marriage unions or linkage
between brothers & sisters
Vertical lines represent offspring; offspring in order LR
oldestyoungest; birth/death dates often included
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Hemophilia
“The Royal Disease”
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Hemophelia: X-linked Inheritance
Pattern
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The incidence of hemophilia is about 1:7,500 live
male births and 1:25,000,000 live female births.
There are about 17,000 people living with
hemophilia in the United States.
As many as 1/3 of the people with hemophilia may
have gotten it from a spontaneous mutation of the
factor VIII clotting gene on their X-chromosome.
The full blown version of factor VIII deficiency is very
rare in women; resulting from having an affected
father and carrier mother
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Genetic Traits & Disorders
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Single Allele Traits: traits determined by a single
allele
Multiple Allele Traits: traits determined by many
alleles
Polygenic Traits: traits determined by more than one
gene
X-Linked Traits: traits coded for on the X
chromosome that have no allele counterpart on the
Y chromosome
Sex-Influenced Traits: traits whose expression is
influenced by sex hormones
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Human conditions/diseases
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Single allele traits (dominant)
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Single allele traits (recessive)
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Hair/skin/eye color, foot size, nose length, height
X-linked traits
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Albinism, cystic fibrosis, phenylketounria, hereditary
deafness
Polygenic traits
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Huntington’s disease, dwarfism, cataracts, polydactyly
Colorblindness, hemophilia, muscular dystrophy, icthyosis
simplex
Multiple allele traits
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ABO blood groups
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ABO Blood Groups
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Three alleles control
blood type: IA, IB, i
Blood types are:
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A, B, or O
Genotype
Blood Type
IAIA
A
IAi
A
IBIB
B
IBi
IAIB
ii
B
AB
O
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Human Genetic Disorders
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Genetic screening
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Genetic counseling
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Test amnionic fluid for genetic defects, protein defects,
karyotype
Chorionic Villus Sampling (wk 8-10)
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Counseling on test results, options
Amniocentesis
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Examine pedigrees, genetic tests
Test chorion villus for genetic defects, karyotype
Post-birth tests
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PKU
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http://en.wikipedia.org/wiki/Phenylketonuria
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Disorders Due to Nondisjunction
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Nondisjunction occurs during meiosis I resulting in
gametes getting no chromosome, an extra
chromosome or a partial piece of a chromosome
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Resultant conditions termed:
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Monosomy – condition in which the human zygote has only 45
chromosomes
Trisomy – conditions in which the human zygote has an extra
chromosome, ie., 47. Sometimes an entire or just a portion of
a chromosome is extra in the genotype
These disorders may happen to either the
autosomes or sex chromosomes
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Autosomal monosomies: all lethal, fetuses spontaneously
abort prior to birth
http://anthro.palomar.edu/abnormal/abnormal_4.htm
Autosomal trisomies: most lethal; only trisomy of
chromosomes # 13, 18, 21 can result in a live birth.
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Autosomal Trisomies:
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Trisomy 13 – Patau Syndrome (1 in 8-12,000 births
US); survival after birth ~3 days to 6 months
Trisomy 18 – Edward’s Syndrome (1 in 3,000 births
US); survival rate after birth ~1-3 days
Trisomy 21 – Down’s Syndrome (1 in 800 births &
6,000 born yearly US);
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Approximately 75% of concepti with trisomy 21 die in
embryonic or fetal life.
Approximately 85% of infants survive to age 1 year, and
50% can be expected to live longer than age 50 years.
http://emedicine.medscape.com/article/943216-overview
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Sex Chromosome Anomalies:
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Sex-chromosome monosomies:
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Turner’s Syndrome, XO (only 1 “X” chromosome)
http://en.wikipedia.org/wiki/Turner_syndrome
Sex-chromosome trisomies:
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Klinfelter’s Syndrome, XXY
http://en.wikipedia.org/wiki/Klinefelter's_syndrome
Supermale Syndrome, XYY
http://en.wikipedia.org/wiki/XYY_syndrome
Superfemale Syndrome, XXX
http://en.wikipedia.org/wiki/Triple_X_syndrome
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Turner’s Syndrome, XO
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Individual is a female
1 out of every 2,500 female live births
worldwide.
Individuals may have major heart defects,
unusually short stature, loss of ovarian
function, webbed neck, coarctation of the
aorta, blocked lymphatic system, kidney
malformation, diabetes, osteoporosis
Individuals have normal intelligence, but may
have difficulty with visual-spatial coordination
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Turner’s Syndrome
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Klinefelter’s Syndrome, XXY
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Individual is a male, having an extra X chromosome
The principal effects are development of small
testicles and reduced fertility
Individuals are susceptible to breast tumors, germ cell
tumors, diabetes, osteoporosis, pulmonary disease,
rheumatoid arthritis
It is the second most common extra chromosome
condition, named after Dr. Harry Klinefelter, an
endocrinologist at Mass General, Boston, MA
The condition exists in roughly 1 out of every 500 to
1,000 males.
It is not inheritable, caused by a single error
(nondisjunction) during gamete formation
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Klinefelter’s Syndrome
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Some examples of affected individuals
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Supermale Syndrome, XYY
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XYY syndrome is characterized by an extra copy of the Y
chromosome in each of a male's cells.
Males with XYY syndrome are sometimes taller than average,
increased risk of learning disabilities, delayed speech and
language skills.
Developmental delays and behavioral problems are possible, but
vary widely among those affected
Most have normal sexual development and are able to conceive
children.
About 1 in 1,000 males are born with an extra copy of the Y
chromosome in each cell. Five to 10 boys with XYY syndrome
are born in the United States each day
Not inheritable, single error (nondisjunction) occurs in gamete
formation
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