Download Genetic Disorders

Heredity: Inheritance and Variation
of Traits
Inheritance and Variation of Traits (LS3A)
Genetic Disorders
Genetics Disorders
• Many disorders in humans are genetic in origin and follow
Mendel’s laws of inheritance.
• These genetic disorders are often controlled by a single
pair of alleles.
Homologous Chromosomes
Meiosis
Locus- Sickle Cell Disease
s
S
s
Fertilization
Egg (ovum)
23 chromosomes
S
8.19-8.20, 9.8-9.10, 9.15, 9.23
Embryo
46 chromosomes
in 23 pairs
Zygote
46 chromosomes
in 23 pairs
S
LIFE SCIENCE DISCIPLINARY CORE IDEAS
S
Sperm
23 chromosomes
Copyright © Rebecca Rehder Wingerden
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Genetics Disorders
• Karyotyping and biochemical tests of fetal cells and
molecules can help people make reproductive decisions.
• Fetal cells can be obtained through (1) amniocentesis…
• Autosomal chromosomes
are those chromosomes
which males and females
have in common.
• Sex chromosomes are
those chromosomes which
determine gender (female
XX and male XY).
• Humans have a total of 46
chromosomes: 22 pairs of
autosomal chromosomes and
1 pair of sex chromosomes.
Amniotic
fluid
withdrawn
Amniotic
fluid
Centrifugation
Fluid
Fetal
cells
Fetus
(14-20
weeks)
Biochemical
tests
Placenta
Uterus
Cervix
Cell culture
A karyotype is simply a picture of a person's chromosomes. In order to get this picture, the chromosomes
are isolated, stained, and examined under the microscope. Most often, this is done using the chromosomes
in the white blood cells. A picture of the chromosomes is taken through the microscope.
Copyright © 2015 Rebecca Rehder Wingerden
Several
weeks later
Karyotyping
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, and
also used for sex determination in which a small amount of amniotic fluid, which contains fetal tissues, is sampled
from the amniotic sac surrounding a developing fetus, and the fetal DNA is examined for genetic abnormalities. A
needle is usually inserted through the mother's abdominal wall, then through the wall of the uterus, and finally into
the amniotic sac. With the aid of ultrasound-guidance, a physician extracts approximately 20ml of amniotic fluid. If
used for prenatal genetic diagnosis, then fetal cells are separated from the extracted sample. The cells are grown in
a culture medium, then fixed and stained. Under a microscope the chromosomes are examined for abnormalities.
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Genetics Disorders
• Ultrasound is also a very helpful diagnostic tool for
examining a fetus.
• …and (2) Chorionic villus.
Fetus
(10-12
weeks)
Several hours
later
Placenta
Suction
Chorionic villi
Fetal cells
(from chorionic villi)
Karyotyping
Some
biochemical
tests
Chorionic villus sampling (CVS), sometimes called "chorionic villous sampling" (as "villous" is the
adjectival form of the word “villus"), is a form of prenatal diagnosis to determine chromosomal or genetic
disorders in the fetus. It entails sampling of the chorionic villus (placental tissue) and testing it for
chromosomal abnormalities, usually with FISH (fluorescence in situ hybridization is a cytogenetic technique
used to staining DNA) or PCR (polymerase chain reaction is a technology in molecular biology used to
amplify DNA samples). CVS usually takes place at 10–12 weeks' gestation, earlier than amniocentesis or
percutaneous umbilical cord blood sampling. It is the preferred technique before 15 weeks.
Copyright © 2015 Rebecca Rehder Wingerden
Ultrasound is an oscillating sound pressure wave with a frequency greater than the upper limit of the human
hearing range. Ultrasound can be used for medical imaging. Ultrasound has been used by radiologists
and sonographers to image the human body for at least 50 years and has become a widely used diagnostic
tool. The technology is relatively inexpensive and portable, especially when compared with other
techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT). Ultrasound is
also used to visualize fetuses during routine and emergency prenatal care. Such diagnostic applications used
during pregnancy are referred to as obstetric sonography. As currently applied in the medical field,
properly performed ultrasound poses no known risks to the patient.
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Genetics Disorders
• Most genetic disorders are caused by autosomal recessive
alleles, i.e. cystic fibrosis and sickle-cell disease.
• Some genetic disorders are caused by autosomal
dominant disorders, i.e. achondroplasia and Huntington’s
disease.
Recessive
Dominant
Aa
Aa
Aa
Aa
aa
aa
A pedigree shows the pattern of inheritance for a particular condition; genetic counselors can use a
pedigree to determine whether a condition is dominant or recessive. Consider the two possible
patterns of inheritance above. In pattern I, the child is affected, but neither parent is; this can
happen if the condition is recessive and both parents are Aa. Notice that the parents are carriers,
because they appear normal (do not express the trait) but are capable of having a child with the
genetic disorder. In pattern II, the child is unaffected, but the parents are affected. This can
happen if the condition is dominant and the parents are Aa.
Copyright © 2015 Rebecca Rehder Wingerden
• Family pedigrees are used to determine patterns of
inheritance and individual genotypes.
Pedigree showing inheritance
of deafness in a family from
Martha’s Vineyard. In the
pedigree, squares represent
males, and circles represent
females; colored symbols here
indicate deafness. The earliest
generation studies is at the top
of the pedigree. Notice that
deafness did not appear in this
generation and that is showed
up in only two of the seven
children in the generation at the
bottom. By applying Mendel’s
principles, we can deduce that
the deafness allele is recessive.
Dd
Joshua
Lambert
D_?
John
Eddy
Dd
Abigail
Linnell
dd
Jonathan
Lambert
?
D_
Abigail
Lambert
Dd
Dd
dd
Male
?
D_
Hepzibah
Daggett
Dd
Elizabeth
Eddy
Dd
Dd
Dd
dd
Female
Deaf
Hearing
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Autosomal Recessive
Genetics Disorders
Autosomal Dominant
• Some genetic disorders are caused by alleles that are
located on the sex chromosomes, i.e. Hemophilia and redgreen color blindness.
• The X sex chromosome is larger than the Y and therefore
carries many alleles that have little to do with gender.
• The inheritance of X-linked genes follow special rules.
*
*
Pseudoautosomal regions are inherited just
like any autosomal genes. Males have two
copies of these genes: one in the
pseudoautosomal region of their Y, the other in
the corresponding portion of their X
chromosome.
How would you know that
the individual at the asterisk
is heterozygous?
Differential regions contain genes which are
not inherited like autosomal genes. This region
makes up about 95% of the Y chromosome
and is the location of the SRY gene. On the X
chromosome the differential region carries
nearly 1,000 genes few of which have
anything to do directly with sex. The
inheritance of these genes follow special rules.
How would you know that
the individual at the asterisk
is heterozygous?
Copyright © 2015 Rebecca Rehder Wingerden
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Genetics Disorders
• A male receives a single X chromosome from his mother
and therefore will have the X-linked disorder if inherited.
Red-green color blindness.
• A female receives two X
chromosomes and therefore
would need to receive the Xlinked disorder from both
parents.
Sex-linked genes exhibit a
unique pattern of inheritance. In
fruit flies eye color is a sexlinked characteristic. The
inheritance pattern of this gene
reflects the fact that males have
one X chromosome and females
have two. These figures
illustrate inheritance patterns for
white eye color (r) in the fruit
fly, an X-linked recessive trait.
Copyright © 2015 Rebecca Rehder Wingerden
Female
XRXR
Male
XrY
XR
Female
XRY
Y
XRY
Xr
XRXR
XrXR
XRY
XrY
R = red-eye allele
r = white-eye allele
Female
Male
XRXr
XrY
XR
XR
Xr
XRXr
Male
XRXr
Xr
XR
Y
Xr
XRXr
XrXr
XrY
XRY
Y
Color blindness, or color vision deficiency, is the inability or decreased ability to see color, or perceive color
differences, under normal lighting conditions. The most usual cause is a fault in the development of one or
more sets of retinal cones that perceive color in light and transmit that information to the optic nerve. This type
of color blindness is usually a sex-linked condition. The genes that produce photopigments are carried on the
X chromosome; if some of these genes are missing or damaged, color blindness will be expressed. Color
blindness will be expressed in males with a much higher probability than in females because males only have
one X chromosome.
Copyright © 2015 Rebecca Rehder Wingerden
Genetics Disorders
Hemophilia
Czar Nicholas II was
the last Emperor of
Russia. He ruled from
1868 to 1917. Political
enemies nicknamed him
Nicholas the Bloody
because of his violent
suppression of the 1905
Revolution. Nicholas II
and his family were
executed by the
Bolsheviks in 1918.
XCXc
XCY
Queen
Victoria
Albert
Do you
recognize
this family?
XCY
XCXc
Louis
Alice
XCY
XCXc
Czar
Nicholas II
of Russia
Alexandra
XcY
Alexis
Hemophilia is a bleeding disorder that slows the blood clotting process. A high incidence of hemophilia has
plagued the royal families of Europe. The two major forms of hemophilia occur much more commonly in
males than in females. Hemophilia A is the most common type of the condition occurring in 1 in 4000 to 1
in 5000 males worldwide. Hemophilia B occurs approximately 1 in 20,000 newborn males worldwide. Both
Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. Hemophilia is less common
in females, because they would need to receive two altered copies of this gene to exhibit the disorder.
Copyright © 2015 Rebecca Rehder Wingerden