Introduction to Genetics / Principles of Genetic Inheretance Flashcards
Define a gene.
A segment of DNA on a chromosome. Each gene occupies, a specific place, or locus/loci.
What is a chromatid?
One of two identical copies of a chromosome.
Sister chormatids vs homologus chromosomes.
- Sister chromatid: one of two identical copies of a chomosome after replication.
- Homologus chromosomes: 2 copies of each gene (one is from your mom the other is from your dad).
What is a centromere?
Connects identical sister chromatids.
What is a telomere?
A region at the end of a chromosome for stability.
Locus
Location of gene
What is a karyotype?
process by which cytogeneticists take photographs of chromosomes in order to determine the chromosome complement of an individual, including the number of chromosomes and any abnormalies.
- Each chromosome in the karyotype is presented as a single condensed or as a duplicated chromosome
- Normal human karyotype is written 46XY (male); 46XX (female)
Genotype meaning
an individual’s genetic makeup
- Homozygous: two identical alleles
- Heterozygous: two different alleles
- The dominant allele dictates the phenotype
- Only a homozygous recessive genotype will affect the phenotype
Phenotype
What is actually observed, ie: physical appearance.
Pleiotropy
the production by a single gene of two or more apparently unrelated effects.
Some alleles are not fully dominant or recessive. Thus any pattern of inheritance in which traits do not segregate in accordance to laws is called __________. Examples include: ________ and _______.
- Mendel’s Laws
- Co dominance
- incomplete dominance
Germ line vs Somatic cells
Germline cells: reproductive cells.
Somatic cells: Any other cells than reproductive cells
All human somatic cells are _______.
Diploid
Autosome
Chromosomes common in both genders (obtained form each parent).
Sex chromosome
X for female, Y for male.
Co dominance
Think of the pink and white flower. Both colors show 50/50.
Allele
Variant form of a given gene. IE (cc, CC, Cc).
What is lyonization?
- It is also called X-inactivation.
- this occurs in females because they have 2 x chromosomes. Thus a random chromsomes is inactivated “turned off”.
Mosacicsm
Two or more populations of cells with different genotypes in a individual who has developed from a single fertilized egg.
- It results from errors in cell divison
Down Syndrome
some 46XX; some 47XX,+21
Klinefelter Syndrome
Some 46 XY, some 47 XXY.
Turner Syndrome
Some 46 XX some 45 XO.
__ gene encodes for betaglobin subunit for hemogobin.
HBB
Thalassemia
- Under production of hemoglobin
- A lack of hemoglobin disrupts the normal development of red blood cells.
- A shortage of mature red blood cells can reduce the amount of oxygen that is delivered to tissues to below what is needed to satisfy the body’s energy needs.
- A lack of oxygen in the body’s tissues can lead to poor growth, organ damage, and other health problems associated with beta thalassemia.
Methemoglobinemia
- More than 10 muations in the HBB gene have been found to cause this
- mutations often affect the region of the protein that binds to heme
Sickle cell anemia
- mutation results in the production of an abnormal version of beta-globin called hemoglobin S or HbS
- Abnormal hemoglobin S subunits to stick together and form long, rigid molecules that bend red blood cells into a sickle (crescent) shape.
- The sickle-shaped cells die prematurely, which can lead to a shortage of red blood cells (anemia).
- The sickle-shaped cells are rigid and can block small blood vessels, causing severe pain and organ damage.
Hemoglobin C
(HbC) disease
- (Glu6Lys mutation), more common in people of West African descent.
- Two Hemoglobin C subunits.
- Chronic anemia and premature lysis of RBCs
Hemoglobin E
- (HbE) disease
- disease (Glu26Lys mutation), more common in people of SE Asian descent.
- Two Hemoglobin E subunits, can occur concurrent with thalassemia and symptoms can range from mild anemia to severe thalassemia.
Stem cell types
Embryonic and adult
Embryonic stem cells
- derived from the embryo and are pluripotent (cabable of becoming any cell type in the body)
Adult stem cells
undifferentiated cells that generate cell types in the tissues in which they reside (hemoatopoetic stem cells will only pro blood cells only)
Stem cell facts
- can diffeentiate into specialixe cells in stanges
- these stanges involve multiple factors that combine to prod epigenetic markers in the DNA to restrict DNA expression and thus the type of cell that the stem cell will diff to
- the DNA expression can be passed to daughter cells through cell divison or daughter cells can reatin their status as a stem cell
Mosaicism
- condition where cells from an individual who has developed from a single fertilzed egg will have different genotype caused by an error in cell division in early embryonic life.
How is mosaicism Dx
chromosoal or microarray analysis
Examples of mosacisicm
- down syndrome (trisomy at chromosome 21)
- klinefelter syndrome
- turner syndrome
*
Fill in the blanks
Explain the following modes of inheritance:
- autosomal dominant
- autosomal recessive
- x linked
- x linked dominant
List the following facts about mitochondiral DNA
- length
- double or single stranded
- circular or linerar
- what does it encode
- where does transcription take place
- does it contain introns or not
- where is it inherited from
- what is the mutation rate
*
–Several copies of 16,569 bp, double-stranded, circular mtDNA molecule per mitochondria
–Encodes rRNA, tRNA, and 13 polypeptides involved in oxidative phosphorylation
–Transcription takes place in the mitochondrion, independently of the nucleus
–Contain no introns
–Inherited exclusively through the maternal line
–Mutation rate is approx. 10x higher than nDNA
- Relative lack of DNA repair mechanisms
- Damage from free oxygen radicals released during oxidative phosphorylation
There are a variety of inherited mitochondrial diseases that are passed on only by mothers, including
Leber heredity optic neuropathy (LHON)
Myoclonic epilepsy and ragged red fibers (MERRF)
Mitochondrial encephalopathy, lactic acidosis and stroke-like activity (MELAS)
Leber herediaty optic neuropathy
•(LHON): due to mutations in genes that encode the subunits of complex I. This results in less active complex I, which presents as acute loss of vision in early adulthood.
Myoclonic epilepsy and ragged red fibers
MERRF
caused by a mutation in the gene or the tRNA for lysine, which disrupts the synthesis of cytochrome-c oxidase. Patients with this conditions display myoclonus dinated muscle movement (ataxia) and seizures.
Mitochondrial encephalopathy, lactic acidosis and stroke-like activity
(MELAS): there is a mutation in the tRNA gene for leucine, which disrupts the synthesis of complex I and cytochrome-c oxidase. This affects the nervous system and muscle function. Patients present with a host of symtoms including severe headaches, seizures, vomiting, and hemiparesis.
Mitosis
- Interphase: chromosome duplication, DNA duplicated
- Prophase: chromosomal condensation (X-shaped). Mitotic spindle forms between centriole
- Metaphase: chromosomes align across the cell
- Anaphase: sister chromatids pulled apart by centrioles to opposite poles
- Telophase and cytokinesis: chromosomes gather at each pole, nucleal membrane forms. Cell divides
Meiosis Steps
- Meiosis I: cell divides twice to form four daughter cells
- Meiosis II: starts with 2 daughter cells with 23 chromosomes each
–4 granddaughter cells formed, each with a half set of chromosomes (haploid)
–Males –> sperm cells
–Females –> one is an egg cell, other 3 are polar bodies (non-reproducing)
Describe the two ways meiosis creates genetic diveristy.
–Random segregation of homologs
–Cross-over exchange (a.k.a. homologous recombination)
Describe the normal name for cells with a normal number of chromosomes and also meiotic errors.
•Euploid: Cells with a normal number of chromosomes
–Ex. Haploid gametes and diploid somatic cells
•Polyploidy: cells contain a complete set of extra chromosomes in a cells
–Often seen in plants
•Aneuploidy: cells contain a missing or additional individual chromosomes
–Monosomy, trisomy
What is the most common cause of aneuploidy and then define the term.
Nondisjunction: The failure of chromosomes to disjoin normally during meiosis
- Can occur during meiosis I or II
- The resulting gamete either lacks a chromosome (monosomic) or has two copies (trisomic)
ADD CORELATION BOXES FROM 366, AND 368.
Pedigree 101
postaxial Polydactyly
example of autosomal dom
-extra finger
Tyrosinase Negative Albinisim
Example of autosomal recessive inheritance
Duchene Muscular Dystrorphy
X linked reccessive (absense of defect of dystrophin, most men essentially paralyzed from the nexck down) Cardiomypotahy is comon with this Sx.
-Sx of this is gowers manuver
Why is the mutation rate higher in MtDNA than nDNA?
-There are no DNA repair mechanisims, also damage from free oxgyen radicals from Ox phos
Define Hetroplasmy and Homoplasmy:
Hetero:
A cell can have some mitochondria that have a mutation in the mtDNA and some that do not.
The proportion of mutant mtDNA molecules determines both the penetrance and severity of expression of some diseases.
Symptoms usually do not develop until adulthood becaue these mutants mitochoddrial alleles must undergo many cell divisions before suffienct amount are present to cause Sx.
Homo:
efers to a cell that has a uniform collection of mtDNA: either completely normal mtDNA or completely mutant mtDNA.
Lebers Hereditary Optic Neuropathy
- LHON
- DEGREDATION of retinal ganglion cells caused by one of three pathogenic mtDNA point mutation affecting NADH dehydrogense
- you have accute or subacute loss of centeral vision and will loose vision in both eyes by early teens/20s
MITOCHONDIRAL DISORDER
What does mtDNA encode?
Where does transcripton of the DNA occur?
Does it contain intron?
What line is it inheretied from?
- encodes rRNA, tRNA and 13 polypeptides for ox phos
- transcriptoon occurs in mitochodnria
- contains no introns
- inherited from maternal line
Myoclonic epilepsy and ragged red fibers
MERRF: mitochondrial disoreder
- caused by muation in gener encoding for tRNA for lysine which disurpts the synthesis of cytochrome C oxidase
- pateints have ataxia and seisures
- affects muslces and nerves
- large variability of presenstaion due to hetroplasmy
Mitochondrial Encephalompathy, lactic acidosis and stroke like eps
MELAS: MITOCHONDRIA DISORDER
- most common matenrlaly inherited disease
- affects many body systems such as nervcous system and muscles
- causes troke and dementia
There is a _____ for mitochondrial hetroplasmy to have Sx.
Threshold
Hypophosphatemia
X linked dominant
- low phosporous in blood due to defective reabsorbtion of phosphate in kidney
- defecicient absorption of ca IN INTESTINES CAUSES SOFTEING OF BONES
- has abnormal vit d metabolism
- treatment oral phsophate and vit d
Define Euploid, polyploid, aneuploidy
- euploid: cells with normal number of chromosomes: haploid gametes (n) and diploid somatic cells (2n)
- polyploidy: cells contain a complete set of extra chromosomes in a cell (often seen in plants)
- aneuploid: sellc contain a mising or additional individual chromosome: monosomy or trisomony
Types of non disjunction
Draw it out
Genomic impriting
- certian genes are only expressed only from mother or father (one is transcriptonally inactive) via the methylation of 5’ region of gene. This causes chromatin condensation.
- epigenetics impirnts remain throughout the lifespan of the individual in somatic cells.
- in germ cells epigenetic imprints are reseat at each generation
UDP
Both chromosomes are from the same parent.
In some cases, however, it does make a difference whether a gene is inherited from a person’s mother or father. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting.
What occurs from UDP?
Prader Willi syndrome, invloves impiritng gene on long arm of chromsome 15
- Inversion
- transloaction
- deletion
- duplactation
inversion: segement of chomsomal DNA is present in reverse orientation
deletion: segment is lost
duplacation: segment is coppied causing aplifcatiaton
- trasnslocation: swap (balanced: where resultant hybrid chromsomes are similar length, or unbalanced (not in syminalr length)
non homologous chromsome recripocral translocation
exhcange of material between two non homolog chromosomes
Robertsonian
long arm of acrocentric chromsomes combined and short arm is lost (occurs with 14/21)
Turner Syndrome
- 45 XO
- female (no Y)
- are infertile, premature ovrain function, 30% have webbed neck, CV defects
Prader Willi
patenral deletion of region of chromsome 15
-Sx short stature, small hands and feet, obeses, cant stop eadting, mild to mod inteletical disability
Angelman Syndrome
- maternal deletion in chromosome 15
- seizures, ataxic gait, sever inellectial disability
Klinefelters syndrom
47 XXY or XXXY,XXXXY
-very tall, infertile, small and or undescended tetes
Down Syndrome
Trisomy 21 (47 XX + 21)
- also due to unbalanced transloaction (14:21)
- cardiac defects, duodenal atresia, abset nasal bone, short limbs, variging degree of cog impairment
Trisomy 18
Edwards syndrome 47 xx + 18
- diagonesd by intrautrine growth restrictions (IURG) : baby isnt growing enough
- 95% die in eurto
Trisomy 13
Patau syndrome (47 xx +13)
Reduced penetrance/ Incomplete penetrance
the % of people who show the gene even though they all have the genotype
ex: Retnoblatoma: autosomal dom
- braca1 or 2 mutation
Variable expressitity
the pheontype ranges for a genotype
-example: neurofibromatosis: spots differe in number, shape, size and poisiton
Marfan Syndrome
-affects the connective tissue and other systems, example of variable expressitivy
Locus heterogenetiy
- single disorder that is caused by a mutation in genes on different chorosomes
- IE: osteogenesis imperfecta
mutations in CoL1a1, COL1A2 CTRA and P3H1 all cause that
OR VS AND
OR ADDITION: WHAT IS THE PROBILITY OF PRODUCING 3 GIRLS OR BOYS
AND MUTLIPLICAITON: WHAT IS THE PROBILIITY OF PRODUCING 3 GIRLS
genomic frequency
number of indiicurals with a given genotype deivded by the toal number of individuals in population
- can be homo dom, homo recessive, hetrozogus
- freuqences are: q^2, p^2, 2pq
Allele frequency
freuqency of occurance or proportion of diff alleles of a patricular gene in a given population
tow possible alleles are dom and recessive
frequencies are p and q
LOOK AT EXAMPLE IN SLID 47
Hardy weinberg
useful to ertimate if you are looking for carriers and you have the allele frequency
p2 + 2pq +q2 = 1
Polygenic
Traits in which variations are thought to be caused by the combo of mutliple genes.
MULTIFCATORIAL INHERETICANCE
Multifactorial
trait is caused by enviromental effects and genetic effects
- follows a normal bel curved
- traits are quntitiative (mesurable)
Disease that do not follow the bell curve distributation have underlying ________. For multifactorial disease that are either present or absent it is thought that a _________ imust be crrosedded before a disease is expresed. Give an example of this and explain it.
Liability disrtibution in mulifactorial inheritance
- treshold of liability
- pyloric stenosis: hyerptohy of muslces between stomach and duodenum: males need less risk genes to show dieases female need more
Recurrence risks of _____ can cahnge substantially from one population to another.
Recurrence risk is ____ if more than one family membember is effected.
- multifactorial disease
- higher
