Genetics and After Midterm Flashcards
Malaria Example
Malaria highly prevalent in Africa
»_space; Caused by a parasite transmitted by mosquitos. Invades mature RBCs (red blood cells)
First line of defense against malaria is genetic: alteration in hemoglobin or glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hemoglobin = oxygen-transport protein
G6PD = critical enzyme that prevents free radical damage in RBCs by converting glucose to ribose-5 phosphate; NADPH produced, protects against build up of free radicals (reactive oxygen species)
G6PD deficiency can lead to premature destruction of RBCs (hemolysis)
However, G6PD-deficient individuals are somewhat resistant to malaria: parasite infects mature RBCs. In G6PD deficiency, RBCs are cleared rapidly before they mature, thus parasite dies as well
Sickle Cell is caused by a one amino acid substitution (glutamate replaced with valine) in hemoglobin
Sickle cell anemia
Changes in hemoglobin structure (due to mutation in the Hb gene) result in distortion of RBC shape from biconcave to half-moon (sickle) shape - Sickle cell anemia
Sickle cells get trapped in capillaries and cannot carry enough oxygen to body tissues. Parasite cannot live in sickle cells because 1) not enough nutrients, 2) body eliminates sickle cells, thus the parasite too.
Hardy-Weinberg Equilibrium Law
Genotype frequencies will remain in equilibrium (stable) from generation to generation in an infinitely large and randomly mating population in the absence of
mutations, migration and immigration of the population, and selection against a genotype
p = fr(A) frequency of dominant allele (A) q = fr(a) frequency of recessive allele (a)
Sum of allele frequencies p + q = 1 (100%)
Genotypic frequencies p2 + 2pq + q2 = 1
p2 = frequency of genotype AA 2pq = frequency of genotype Aa (carriers) q2 = frequency of genotype aa
Multiple Alleles: ABO Blood Groups
Multiple alleles: 3 or more alleles of the same gene
When multiple alleles exist, an individual diploid organism still inherits only 2 alleles
Example: ABO blood groups
ABO blood group system was discovered in 1901 by
Karl Landsteiner
Significant for blood transfusions: ABO incompatibility
between donor and recipient can result in life threatening situations
4 different blood groups/types: A, B, AB, and O
Each blood group characterized by the presence of an antigen on the surface of RBCs and the absence of its corresponding antibody in the serum
Different blood types due to different glycoproteins (sugars) on the surface of RBCs. Individuals inherit the gene which codes for the sugars to be added to the red cell
»_space;>A allele codes for an enzyme (transferase) that
adds N-acetylgalactosamine to the terminal sugar
> > > B allele codes for an enzyme (transferase) that
adds D-galactose to the terminal sugar
Landsteiner’s Law
If an individual possesses an ABO antigen, must not have the corresponding antibody
If an individual lacks an ABO antigen, must have the corresponding antibody
Type A – A antigen present; has anti-B
Type B – B antigen present; has anti-A
Type O – no antigen present; has both anti-A and anti-B
Type AB – A and B antigen present; has neither anti-A nor anti-B
Inheritance
IA and IB are dominant in a homozygous or heterozygous state
Both IA and IB are dominant to IO which is recessive
Both IA and IB are co-dominant to each other
AA or AO = Type A Classic Dominance
BB or BO = Type B Classic Dominance
OO = Type O Homozygous Recessive
AB = Type AB Co-Dominance
Hemolysis: If an individual is transfused with an incompatible blood group, destruction of the red blood cells will occur. This may result in the death of the recipient.
Rhesus (Rh) Blood Group System
most important blood group system after ABO
consists of 50 defined blood-group antigens. Most important are D, d, C, c, E and e
Rh system controlled by 2 closely linked genes: RHD and RHCE: Rh gene complex. (One Rh gene complex inherited from each parent)
RhD codes for presence of D antigen on the red blood cell surface (Rh+).
Rh+ individuals may be homozygous DD or heterozygous Dd
“d” is non-functional and produces no antigen (Rh-) - dd
all Rh- individuals must receive Rh- blood.
Production of Ab to D requires exposure to the antigen. A person with Rh- blood does not have Rh Abs naturally in the blood plasma
RHCE gene codes for presence of C, c, E, and e
At the RHCE gene locus, depending on the allele present, one of four antigenic combinations are produced: ce, Ce, cE or CE.
C or c --- co-dominant D or d --- classic dominance E or e --- co-dominant Most common Rh+ = CDe/CDe Most common Rh- = cde/cde
Any and all combinations are possible
Only D confers Rh+ blood
Hemolytic disease of the newborn (erythroblastosis fetalis)
If a Rh- mother during pregnancy is exposed to Rh (D) antigen, she will produce antibodies to this antigen that can cross the placenta and destroy Rh (D) positive fetal cells, resulting in death of the fetus
Preventive treatment = RhoGam Therapy (prevents mother from producing antibodies by binding to fetal Rh+ antigen)
Intrauterine fetal monitoring with repeated ultrasound examination and amniocentesis
Fetus Rh+:
Intrauterine blood transfusion of ‘Rh-’ blood into the baby’s circulation
Exchange transfusion to the baby after birth
In cases of severely sensitized women, medical termination of pregnancy is considered
Mendel’s Pea Plants
The pea plants’ traits were often similar to their parents (purebred)
However, sometimes they showed obvious differences in these traits
The passing of traits from parent to offspring is called heredity
Experiment: He cut away the pollen-bearing male parts of a flower and dusted that flower with pollen from another plant
Followed F1 generation and then let F2 generation self pollinate and noticed that 3/4 of seeds were yellow and 1/4 were green, even if none of the parents were green.
Conclusion: individual factors must control the inheritance of traits that exist in pairs and remain separate instead of blending
they come in alternative versions resulting in variations in inherited characteristics, e.g. yellow peas and green peas
*genetic characteristics (such as height, color, shape, etc) are controlled by unit factors that exist in pairs and they are inherited as a unit
Mendel’s First Law of Segregation
During gamete formation, the paired unit factors (genes) for a specific trait separate (or segregate) randomly into their two alleles (MEIOSIS), so that each gamete receives one or the other with equal likelihood.
At fertilization, the two alleles – one from each parent – unite randomly.
Monohybrid cross
inheritance of a single trait
Ex) AA x Aa
Genotype = 1:1 (either AA or Aa) Phenotype = all dominant
Aa X Aa
Genotype = 1:2:1 ( 1 AA, 2 Aa, 1 aa)
Phenotype = 3:1 (3 dom, 1 recess)
Dihybrid cross
inheritance of 2 traits together
Ex) Yellow and Round seeded plants (YyRr) X Yellow and Round seeded plants (YyRr)
Genotypic ratio: 1YYRR 2YYRr 2YyRR 4YyRr 1YYrr 2Yyrr 1yyRR 2yyRr 1yyrr Phenotypic ratio: 9:3:3:1 9 yellow-round 3 yellow-wrinkled 3 green –round 1 green wrinkled
Mendel’s Second Law of Independent Assortment
the two alleles for seed color segregate independently of the two alleles for seed shape, producing four different pea phenotypes: yellow-round, yellow-wrinkled, green-round, and green-wrinkle
Therefore, each character is independently inherited
During gamete formation, segregating pairs (alleles) of unit factors (genes) assort independently of each other
genes for different traits are inherited independently of each other if they are on different chromosomes
Linkage
Linked genes cannot undergo independent assortment
Linkage: the failure of two genes to assort independently can occurs when genes are close to each other on the SAME chromosome and are inherited as a unit The closer the loci of the genes on the chromosome, the tighter the linkage
However, genes far apart from one another on the same chromosome can assort independently because
of recombination
Recombination (crossing over) = process in which exchange of genetic information occurs between 2 homologous chromosomes during meiosis
The frequency of crossing over (recombination rate) between any 2 loci on a single chromosome is proportional to the distance between them
The maximum rate of recombination is 50%
**A recombination frequency «_space;50% between 2 genes shows that they are linked***
A recombination frequency of 50% (1:1:1:1:1) shows that the transmission of 2 linked genes is indistinguishable from that of two un-linked, independently assorted genes
Example of linked genes
2 closely linked genes control the expression of ALL Rh antigens: RhD gene & RhCE gene
The genotype is determined by the inheritance of 2 pairs of 3 alleles
Each locus on each chromosome has its own set of alleles which are Dd , Cc , and Ee
There are 8 gene complexes at the Rh locus
CDe, Cde , cDE, CdE, cDe, cdE, CDE, cde
Double Crossovers
2 crossovers both occurring between the two loci being examined
First crossover changes the parental configuration of alleles to the recombinant configuration
Second crossover changes the recombinant configuration back to the parental
The net result is that the genes are in the parental configuration, SAME AS IF NO CROSSOVERS HAD OCCURED
Thus, any even number of crossovers is the same as 0 crossovers, and any odd number is the same as 1 crossover
Since we only see the offspring and not the actual crossovers, it is very easy to undercount the number of crossovers that occurred
The further apart 2 genes are, the more likely it is that undetected double crossovers will occur between them
Interference
Interference (I) is the phenomenon through which a crossover event in one region of a chromosome influences (inhibits) the occurrence of a crossover in an adjacent region of the chromosome
Interference is measured by calculating the coefficient of coincidence (C)
Crossovers in adjacent chromosome regions are usually not independent. This interaction is called interference.
A crossover in one region usually decreases the probability of a crossover in an adjacent region.
Inference = 1 - (observed # of double recombinants)/ (expected # of double recombinants)
SRY gene
Sex-determining region of the Y chromosome
Located near the end of the short arm of the Y chromosome
Plays a major role in causing the undifferentiated gonad to develop into a testis
Patterns of Inheritance
Autosomal Dominant:
affected individuals have an affected parent
either sex affected:
Familial hypercholesterolemia
Huntington disease
Neurofibromatosis
Marfan syndrome
Von Hippel-Lindau disease
Autosomal Recessive:
affected individuals usually have un-affected (carrier) parents either sex affected
Sickle cell anemia
Cystic fibrosis
Phenylketonuria
X-linked Dominant:
affected individuals have an affected parent of either sex affected; No male-to-male transmission!!!!
Fragile X syndrome
Hypophosphatemic rickets
X-linked Recessive:
affected individuals usually have un-affected (carrier) parents either sex affected (mother); No male-to-male transmission
Duchenne muscular dystrophy
G-6-PD deficiency
Hemophilia A and B
Mitochondrial Inheritance:
Inherited maternally because only mother contributes mitochondria during conception
Either sex affected
Usually neuropathies and myopathies because brain and muscle are highly dependent on oxidative phosphorylation
Sex-Linked Inheritance
Sex-linked trait: Traits only found on the X chromosome
Sex-linked disease: Disease or syndromes caused by recessive genes located on X-chromosome
Female -
Homozygous = disease
Heterozygous = variable expression (carriers)
Male – hemizygous
X linked alleles always show up in males whether dominant or recessive because males have only one X chromosome
EXAMPLES!!!!!!!!!!!!!!!!!!!!
Colorblindness: inability to distinguish the differences between certain colors
most common type is red-green colorblindness, where red and green are seen as the same color
Color vision genes are located on X chromosome
Hemophilia (The Royal disease): inability of blood to clot
absence of clotting factors VIII and IX, located on X chromosome
prolonged bleeding time in affected individuals can lead to death
Sex-linked Syndromes
of chromosomes is not an exact multiple of the haploid set -aneuploidy’
XO – Turner’s Syndrome (45 chromosomes, missing one X)
YO – Lethal Mutation
XXY – Klinefelter’s Syndrome (47 chromosomes, extra X)
XYY – Jacobs Syndrome (47 chromosomes, extra Y)
XXX – Triple X Syndrome (47 chromosomes, extra X)
Multiple XY – more than 2 X with a Y – like Klinefelter’s syndrome
Sex Influenced Traits
When the sex of an individual influences the expression of a phenotype that is not limited to one sex or the other.
Traits controlled by autosomal genes that are usually dominant in one sex but recessive in the other sex e.g. Pattern baldness
(Acts like a dominant trait in males and a recessive trait in females; different testosterone levels)
Sex-Limited Traits
When the expression of a specific phenotype is absolutely limited to one sex
Traits expressed only in females because males die before birth
Example: Male-lethal X-linked dominant traits such as Rett syndrome
Traits expressed only in males
Example: Duchenne muscular dystrophy (X-linked recessive); life expectancy 25 years
-Therefore X recessive not passed on from father onto daughters, very rare in females
Causes of Mutations
Substances Inducing Mutations
- Mutagens (Substances that alter DNA structure in various ways and can cause DNA damage; cause bases to mispair and bond with the wrong base (most common mutation); like UV light and chemicals like Benzene)
- Teratogens (Agents that cause harm or birth defects to an embryo or fetus)
- Carcinogens (Chemicals or ionizing radiation that cause or promote cancer)
Aneuploidy
of chromosomes is not an exact multiple of the haploid set (related to increasing maternal age)
Monosomy
Monosomy – loss of a single chromosome from a diploid genome (2n - 1 chromosomes)
Trisomy
gain of one chromosome from a diploid genome (2n + 1 total chromosomes)
Euploidy
of chromosomes is exact multiple of the haploid set
humans are euploidy
Polyploidy
more than 2 complete sets of chromosomes
Triploid
one extra complete set of chromosomes (3n)
Tetraploid
2 extra complete sets of chromosomes (4n)
Cause of numerical chromosome abnormalities
Nondisjunction =
cell division error in which homologous chromosomes fail to separate during segregation in meiosis I or the sister chromatids of a chromosome fail to separate during meiosis II or mitosis
Consequence of nondisjunction: imbalance in the number of chromosomes, one daughter cell has two chromosomes or two chromatids, and the other has none
Mosaicism
presence of different chromosome constitution (karyotype) within cells of a single individual
condition in which a tissue may contain cells that have some chromosome abnormality and other cells with normal karyotype
females are naturally mosaics for genes on the X chromosome because one X chromosome (paternal or maternal) in every cell is randomly inactivated (Barr body). Therefore, some cells express maternally-derived and others paternally-derived alleles
Types of numerical chromosomal abnormalities
Sex chromosome abnormalities
Autosomal (non sex-linked) chromosome abnormalities
Turner’s Syndrome
XO – Turner’s Syndrome (45 chromosomes, missing one X)
CLASSIFIED AS FEMALE
Most XO fetuses die before birth
Surviving individuals are females – 1 in 5,000 female births
noticeable at puberty, when secondary sexual characteristics fail to develop
immature ovaries- sterile poorly developed breasts short stature webbed necks heart problems retardation unaffected lifespan
Klinefelter’s syndrome
(XXY, 47 chromosomes)
CLASSIFIED AS MALE
Male – incidence 1 in 1,000 male births Small testes, low testosterone - sterile Breast development in about 50% of XXY individuals Sparse facial hair Subnormal intelligence in some cases 48, XXXY 49, XXXXY
Jacobs Syndrome (XYY)
Jacobs Syndrome (XYY)
Male – 1 in 1,000 male births
Excessively tall
sometimes retardation – not severe
usually fertile but sometimes fertility affected
antisocial behavior patterns e.g. sociopathic, aggressiveness
Trisomy X (XXX)
Females – 1 in 1,500 female births usually normal underdeveloped secondary sex characteristics sterility mental retardation
Autosomal chromosome abnormalities
Monosomies – loss of one chromosome (2n - 1) – lethal
Trisomies – addition of an extra chromosome (2n + 1):
Down Syndrome – Trisomy 21
Patau Syndrome – Trisomy 13
Edwards Syndrome – Trisomy 18
Down Syndrome
Caused by an extra chromosome 21 (trisomy 21);
nondisjunction in meiosis I;
father contributing extra chromosome in 15% of cases
The incidence of trisomy 21 is about 1 in 800 live births but SHARPLY INCREASES WITH MATERNAL AGE
Patau Syndrome
Trisomy 13
Incidence 1 in 15,000 live births; maternal disjunction
50% of these babies die within the first month, 90% die within the first year, and very few survive beyond the first year
multiple dysmorphic features: Small head Small or missing eyes Cleft lip/palate Extra fingers Heart defects Abnormal genitalia Severe developmental and mental retardation
Edwards Syndrome
Trisomy 18
90% die within the first year, and very few survive beyond the first year
The surviving individuals have severe mental and developmental retardation
Small face
Small sternum
**Clenched fingers and toes*****
