MT6315 L2 MENDELIAN AND NON-MENDELIAN Flashcards
Genetics is a branch of biology what deals with?
heredity and variation
What carries hereditary information?
Chromosomes
T or F: Homologous chromosomes contain the same genetic information
F; only look alike but different information and contain the DNA that codes for the same genes but different ‘versions’
What are sister chromatids?
exact replicas
What is a gene?
unit of heredity; a section of DNA sequence
encoding a single protein
two genes that occupy the same position on homologous chromosomes and that cover the same trait
Alleles
What is a genome?
the entire set of genes in an organism
a fixed location on a strand of DNA where a gene or one of its alleles is located.
Locus/Locii (plural)
How many autosomal chromosome pairs are there?
22
Dominant genes occur in what conditions?
Heterozygous
Single pair genetic cross
Parents differ by a single trait
Monohybrid cross
What are single gene diseases? Mendelian or Non mendelian?
Mendelian
What type of phenotype is the most common expression of a particular allele combination in a population?
Wild type
T or F: Wild type may be recessive or dominant.
T
phenotype is a variant of a gene’s expression that arises when the gene undergoes
a change
Mutant phenotype
What is an illness that causes uncontrollable movements and changes cognition?
Huntington’s disease
HD is dominant or recessive?
Dominant
T or F: Each child of an affected individual need inherit only one copy of the mutant gene to develop the disease.
T
T or F: An inherited disease affects each child independently.
T
What is autosomal dominant inheritance?
Inheritance in the same way regardless of sex
How do you deduce the probability that a particular person has inherited a single-gene disease?
considering how he or she is related to an affected relative.
tests can sometimes predict the risk of developing symptoms.
T or F: Single genes are specific in commonality in certain populations.
Common in some populations than others
Why do mutations stay in certain populations?
because we tend to have children with people similar to ourselves.
Examples of single-gene disease?
sickle cell disease and muscular dystrophy
Many phenotypes associated with single genes are influenced by _____ and _______
other genes as well as by environmental factors
The single gene controls?
trait transmission and other genes and the environment affect the degree of the trait or severity of the illness
What is the test of trios?
sick children and their parents can reveal whether the child inherited two disease-causing mutations from carrier parents, or whether a dominant mutation arose anew, termed “de novo.”
Before Mendel, what was the thought of inheritance?
Blending theory - traits blend together and are inherited by offspring
What are the traits Mendel observed in pea plants?
Seed form
Seed color
Pod form
Pod color
Flower position
Seed coat color
Stem length
Why did Mendel choose pea plants?
easy to grow, develop quickly, and have many traits that take one of two easily distinguishable forms.”
What is Mendel’s theory?
Particulate theory of inheritance aka Gene idea
Inheritance involves the passing of discrete units of inheritance, or genes, from parents to offspring.
What is the Chromosome Theory of Inheritance and who proposed it?
Sutton and Boveri using fruit flies
Genes are present within chromosomes inside the cell
Genes and chromosomes are in pairs in diploid cells
What are the principles of the pattern of inheritance?
- Principle of Dominance
- Principle of Independent Assortment
- Principle of Segregation
What principle: When gametes are formed, the pairs of hereditary factors (genes) become separated, so that each sex cell (egg/sperm) receives only one kind of gene.
Principle of Segregation
Mendel noted that short plants crossed to other short plants were?
true breeding - producing the same phenotype all the way due to homozygous recessives
Some dominantly inherited diseases are said to be due to?
gain of function - result from the action of an abnormal protein that interferes with the function of the normal protein.
Huntington disease results from a gain-of-function in which?
dominant mutant allele encodes an abnormally long protein that prevents the normal protein from functioning in certain brain cells.
protein encoded by the mutant HD allele must be abnormal, not absent, to cause the disease.
What does the gain of function do?
ADDS activity to alter the encoded protein
T or F: The gain-of-function nature of HD is why people with one mutant allele have the same phenotype as the rare individuals with two mutant alleles.
T
Why do dominant diseases persist in populations?
because they do not prevent a person from having children and passing on the mutation.
What gene confers eye color?
OCA2 on chromosome 15 by controlling melanin synthesis
If OCA2 gene is missing, what happens?
Albinism occurs
What does recessive and dominant OCA2 confer?
Dominant - brown eyes
Recessive - blue eyes
What causes blue eyes?
HERC2 recessive allele abolishes control over OCA2
2 copies of recessive allele in HERC2 to have blue eyes
T or F: Under certain circumstances, for some genes, a homozygous individual can develop symptoms.
F; heterozygous
What sickness?
Carriers can develop a life- threatening breakdown of muscle if exposed to the combination of environmental heat, intense physical activity, and dehydration.
Sickle cell disease
What is compound heterozygosity?
An individual with two different recessive alleles for the same gene
Inherited diseases are CH
How is nucleotide inheritance determined?
laboratory-based: 10X Genomics or fosmid pool-based strategy
computer-based: SHAPEIT2, Beagle, Eagle2, HapCUT2
What are common Compound Heterozygous diseases?
Phenylketonuria
Tay-Sachs
Sickle cell
first genetic disorder for which mass post-natal
genetic screening was available, beginning in the early 1960s, atypical cases were detected almost
immediately.
Phenylketonuria
In PHENYLKETONURIA, molecular analysis of the genome was not yet possible, but ________revealed
cases caused by compound heterozygosity.
protein sequencing in phenylketonuria
Tay-Sachs is a result of compound heterozygosity between?
two alleles, one that causes the classic infantile disease in homozygotes and another that allows some residual HEXA enzyme activity.
Sickle cell disease is a result of?
result from inheritance of the sickle cell gene in a compound heterozygous manner with other mutant beta globin genes.
In the case of sickle cell anemia, an individual with one allele for hemoglobin S and one allele for hemoglobin C would still develop the disease, despite being heterozygous for both genes.
Recessive traits arise from?
loss of function - prevents the production or activity of the normal protein
What is the inborn error of metabolism?
diseases are typically recessive because the half normal amount of the enzyme that a carrier produces is usually sufficient to maintain health.
The one normal allele, therefore, compensates for the mutant one, to which it is dominant.
What is more severe, dominant or recessive diseases?
recessive
Why do disease-causing recessive alleles remain in populations?
healthy -heterozygotes pass them to future
generations
What kind of genetic diseases are transmitted silently? How?
autosomal recessive and unexpectedly
via heterozygotes (carriers)
What conditions serve as a more likely occurrence of autosomal recessive being passed on to the next generation?
Consanguinity
Autosomal Dom or Recessive: Males and females equally affected
Auto dom
Autosomal Dom or Recessive: skips generations
Auto Rec
Autosomal Dom or Recessive: passed on until no one is affected
Auto dom
Autosomal Dom or Recessive: Affected person has affected parents unless there is de novo
Auto dom
Autosomal Dom or Recessive: parents can be affected OR carriers
Auto rec
The law of segregation reflects the actions of chromosomes and the genes they carry during ______.
meiosis
What is non-true breeding?
heterozygous
T or F: Gametes combine non-randomly,
F; random
T or F: Two genes that are far apart on the same chromosome also appear to independently assort, because so many crossovers take place between them that it is as if they are part of separate chromosomes
T
What kind of analysis is associated with the Law of Dominance?
Test cross or Pedigree Analysis
What analysis is associated with independent assortment?
Dihybrid cross
What analysis is associated with segregation?
Punnett square – single test cross/monohybrid
Looks like a windowpane
Used to determine the probability of outcome of offspring
Punnett
a lethal genetic disease affecting Caucasians.
Cystic Fibrosis
a fatal genetic disorder that causes the progressive & breakdown of nerve cells in the brain
HD
HD is also known as? Why?
known as the quintessential family disease because every child of a parent with HD has a 50/50 chance of inheriting the faulty gene autosome
When you have an individual with an unknown genotype, you do a_____
test cross.
Test cross: Cross with a ______individual.
homozygous recessive
In Non-Mendelian Genetics, when genes are closer to each other on the chromosome, why does their expression not support Mendel’s predictions?
usually do not segregate at random during meiosis
Instead, genes close on a chromosome are packaged into the same gametes and are said to be “linked”
transmission of genes on the same chromosome.
Linkage
Linked genes do not _____ and do not produce Mendelian ratios for crosses tracking two or more genes.
assort independently
Thomas Morgan identified more than _____ genes on what species of fruit fly?
50 genes on Drosophila’s 4 pairs of chromosomes
Linkage maps first discovered by?
Alfred Sturtevant – student of Thomas Morgan
What is a linkage map?
map based on frequencies of recombination between markers during crossover of homologous chromosomes
What is linkage mapping?
based on linkage analysis
shows relative position, as determined by how after 2 gene loci are inherited together
Is crossing over likely for each gene in the genetic maps? Why/ why not?
No because the distances are just estimates
What is linkage disequilibrium?
nonrandom association between DNA sequences
Where are LD blocks interspersed?
Where crossing over is prevalent
What are LD blocks called and what are their uses?
haplotypes – combination of alleles at multiple linked loci which are transmitted together
Haplotype is a portmanteau of what word?
Haploid genotype
In another meaning, what is a haplotype?
set of single nucleotide polymorphisms (SNPs) that are statistically associated
Sex-related genetics includes?
sex-linked trait, sex-limited trait, and sex-influenced trait.
Sex determination depends on the existence of which chromosome?
Y
Males with translocation of the gene can have chromosomes __
Females with mutation of the gene can have chromosomes of __
XX
XY
Why are Y-linked traits rare?
because the chromosome has few genes, and many of its genes have counterparts on the X chromosome.
Y-linked traits are passed from male to male or male to female?
male to male because females have no Y chromosomes
No other Y-linked traits besides ____ are yet clearly defined.
infertility
Some traits at first attributed to the Y chromosome are actually due to?
genes that have been inserted into that chromosome from other chromosomes, such as a deafness gene
What are the parts of the Y chromosome?
PAR1
SRY
Kinase (cell cycle control)
Tooth enamel formation
Bone development
Sperm development
AZF (azoospermia factor)
PAR2
What is the SRY gene?
provides instructions for making a protein called the sex-determining region Y protein.
Sex-linked traits are more likely _____-linked
X
How much percent does X-linked genes account for in single gene disease?
10%
In females, X-linked traits are passed just like _______ traits
autosomal
T or F: Males need 2 copies of the X-linked trait
F; a single copy of an X-linked allele causes expression of the trait or illness because there is no copy of the gene on a second X chromosome to mask the effect.
Who does the male inherit the X link trait from?
His mother
he human male is considered _____ for X-linked traits
hemizygous
X-linked Rec or Dom: expressed in male always
X linked Rec
X-linked Rec or Dom: male to all daughters but no sons
X liked dom
X-linked Rec or Dom: expressed in females in only one copy
X linked dom
X-linked Rec or Dom: males inherit from homo or heterozygote mother
X linked rec
X-linked Rec or Dom: female inherits from affected father and affecter or heterozygote mother
X linked Rec
X-linked Rec or Dom: more severe
X linked dom
X-linked Rec or Dom: expressed in female homo and rarely in female heterozygote
X linked rec
Example of X-linked recessive trait disease?
Hint: blood clotting
hemophilia B is also known as Christmas disease and factor IX (“FIX”) deficiency.
Examples of X-linked dominant disease?
Rett Syndrome
Incontinentia pigmenti
Coffin Lowry Syndrome
Epilepsy with mental retardation (EFMR)
What is Rett Syndrome?
rare neurodevelopment disorder
progressive not degenerative
longevity into adulthood
cannot speak, use hands, walk, eat , breathe easily
seen in females
What are sex limited traits?
affects a structure or function of the body that is
present in only males or only females.
expression of these traits are limited so that normally only one sex is affected.
Example of sex limited traits?
Lactation
What is the male’s contribution in the development of pre eclampsia?
a man who fathered two consecutive women who developed severe preeclampsia and passed away, suggesting the existence of a “fatal father factor.”
male genome may play a role by contributing to the development of supportive structures, such as the placenta.
Example of sex influenced traits?
Baldness
If a male has __ recessive allele, he will show that trait, but it will take___ recessive for the female to show that same trait.
one; two
T or F: When transmission patterns of a visible trait do not exactly fit autosomal recessive or autosomal dominant inheritance, Mendel’s laws are no longer operating.
F; still operating
T or F: Lethal genotype can cause death even before the individual can reproduce.
T
Example of Lethal genotype?
Achondroplastic dwarfism
Is Achondroplastic dwarfism autosomal dominant or autosomal recessive?
Autosomal dominant
What is autosomal dominant transmission?
One copy of the gene will lead to the expression of the disease
Are homozygote individuals for autosomal dominants seen often?
No so it is presumed lethal
type of relationship between alleles, with a heterozygote phenotype intermediate between the two homozygote phenotypes
Incomplete Dominance
Why does Tay Sachs display complete dominance?
heterozygote (carrier) is as healthy as a homozygous dominant
Why is the heterozygote carrier for Tay Sachs as health as homozygous dominant individual?
Hetero has intermediate level of enzymes between full enzyme level and no enzyme and half the amount of enzymes is enough to maintain normal health making wild type allele dominant
What is an example of incomplete dominance?
Familial Hypercholesterolemia (FH)
What happens in FH?
A person with two disease-causing alleles does not have receptors on liver cells that take up the low-density lipoprotein (LDL) form of cholesterol from the bloodstream, so it builds up.
In FH, A person with one disease-causing allele has ____ the normal number of receptors.
half
individuals with_______ die in childhood of heart attacks, those with _______ may suffer heart attacks in young adulthood, and those with ______ do not develop this inherited form of heart disease.
two mutant alleles
one mutant allele
two wild type alleles
What is co dominance?
different alleles that are both expressed in a heterozygote
Example of co dominance?
ABO blood group
when one gene masks or otherwise affects the phenotype of another.
refers to interaction between different genes, not between the alleles of the same gene.
Epistasis
In epistasis, the gene that affects the expression of another is?
Modifier gene
What happens in epistasis?
In epistasis, the blocked gene is expressed normally, but the protein product of the modifier gene inactivates it, removes a structure needed for it to contribute to the phenotype, or otherwise counteracts its effects.
Examples epistasis?
Albinism and Bombay phenotype
What happens in an individual with Bombay phenotype?
A person of genotype hh can’t make the H gene, so the A and B antigens cannot attach to red blood cell surfaces.
The A and B antigens fall off and the person tests as type O, but may be any ABO genotype.
How many percent of the population are Bombay phenotype and who can donate to them?
0.004%
Bombay to Bombay only
A single-gene disease with many symptoms, or a gene that controls several functions or has more than one effect,
Pleiotropy
Example of Pleiotropy?
Marfann Syndrome
What is Marfann syndrome?
autosomal dominant condition is a defect in an elastic connective tissue protein called fibrillin.
The most serious symptom is a weakening in the aorta, which can suddenly burst. If the weakening is detected early, a synthetic graft can replace the section of artery wall and save the person’s life.
Mutations in different genes that produce the same phenotype
Genetic Heterogeneity
When does Genetic Heterogeneity occur?
when genes encode enzymes or other proteins that are part of the same biochemical pathway, or when proteins affect the same body part
Example of genetic heterogeneity?
Osteogenesis imperfecta
OI is caused by what kind of mutations?
autosomal dominant
OI causes?
Mutations in the type 1 collagen genes, COL1A1 and COL1A2 can cause the body to make either abnormally formed collagen or too little collagen. Mutations in these genes cause OI Types I through IV.
What happens to the remaining cases of OI?
caused by autosomal recessive mutations in any of six genes (SERPINF1, CRTAP, LEPRE1, PPIB, SERPINH1, and FKBP10) that code for proteins that help make collagen.
environmentally caused trait that appears to be inherited
Phenocopies
How do Phenocopies work?
can either produce symptoms that resemble those of a known single-gene disease or mimic inheritance patterns by affecting certain relatives.
Example of phenocopy disease?
Thalidomide vs Phocomelia
______ genes regulate organ development.
_____ genes determine the identities of each
body segment.
_______ genes code for transcription factors.
Homeotic
Hox
Homeobox
History behind thalidomide use?
meant as a sleeping aid but prescribed to
pregnant women to treat anxiety and nausea
caused serious birth abnormalities
percentage of individuals who have a particular
genotype who have the associated phenotype.
Penetrance
severity of a phenotype, or the extent to which the gene is expressed.
Expressivity
T or F: HD is completely penetrant
F; almost
T or F: Complete penetrance is rare.
T
HD is caused by?
CAG repeat expansion in the huntingtin gene (HTT). For those with 40 or more CAG repeats, penetrance is 100%,
inheritance of a trait governed by more than one genes.
Polygenic traits
Example of polygenic disorder?
Type 2 diabetes mellitus - multiple genes located on different chromosomes contributing to its susceptibility.
What chromosomes affect: ALL
Philadelphia chromosome
What chromosomes affect: BCR-ACL FUSION
PHILADELPHIA
What chromosomes affect: AML
13
What chromosomes affect: WILLIAMS BEUREN SYNDROME
7
What chromosomes affect: PARATHYROID TUMOR
11
What chromosomes affect: WILMS TUMOR
11
What chromosomes affect: BURKITT LYMPHOMA
8 AND 14
What gene anomaly: CF
DELETION
What gene anomaly: HEMOPHILIA
INVERSION
What gene anomaly: CHARCOT MARIE TOOTH
DUPLICATION
What gene anomaly: DOWN SYNDROME
TRANSLOCATION
What gene anomaly: CML
TRANSLOCATION
