Module 6 - Genetics Flashcards
Gene
section of a DNA molecule
has the biochemical instructions for cells
Genetic information, stored in the structure of DNA, determines what things?
Directs cell structure and day to day cell function
determines appearance
environment response
unit of inheritance
disease susceptibility
how we react to drugs/medications
Genome
total genetic content
Human genome has about 20,300 protein encoding genes
The genome is __% the same in all people
99.9%
the 0.1% difference accounts for individual trait differences
___ create much of our identity
Proteins
Genetic information survives through what 3 things?
- Cell division
- Cell Renewal
- Tissue growth
DNA can ___
replicate
DNA converts to mRNA via ___
transcription
RNA makes proteins via ___
translation
What is the structure of Deoxyribonucleic Acid (DNA)?
Large stable macromolecule
Double helix and base pairing
“spiral staircase with the paired bases resembling steps”
It is a long double stranded helical molecule composed of nucleotides
Where is DNA primarily found?
Mostly in the nucleus but mtDNA is found in the mitochondria
What makes up a Nucleotide in DNA
Phosphoric Acid + 5 Carbon Sugar Deoxyribose _ 1 of 4 nitrogenous bases
2 Kinds of Nitrogenous Bases
Purines and Pyrimidines
Purines
2 nitrogen ring structures
- Adenine
- Guanine
Pyrimidines
Have one nitrogen ring
- Thymine (and Uracil)
- Cytosine
What are the complementary base pairs in DNA and RNA?
A-T (DNA only)
A-U (RNA only)
G-C
Nucleotide
single building block of DNA
Nitrogenous Bases
The basic structure of DNA and carry genetic information in 2 groups (purines and pyrimidines)
How many strands are there after DNA replication?
2 strands become 4 strands
What is the backbone of DNA?
alternating groups of sugars and phosphate with paired nitrogenous bases projecting inwards from the sides of sugar molecules
mtDNA
mitochondrial DNA
Mitochondria have their own DNA, different from that of the nucleus
What is the structure of mtDNA
packaged in a double stranded CIRCULAR chromosome
How is mtDNA passed on?
from mother to children
*so all mtDNA disorders come from the mother, not the father
What does mtDNA code for and why?
Codes for enzymes involved in oxidative phosphorylation reactions
without it/if mutated oxi phos cannot occur leading to energy and ATP abnormalities
Which kind of DNA can repair itself and which cannot?
DNA - can
mtDNA cannot repair itself
Mutations of mtDNA tend to cause dysfunction in what?
tissues with high utilization of ATP (ex: nerve, kidney, muscle, liver)
What is linked to aging?
mtDNA
What mutates more rapidly, DNA or mtDNA
mtDNA
What kind of genetic information is more likely to remain after extensive damage due to the sheer amount of copies there are?
mtDNA
Chromosomes
visible only ion dividing cells
they are tightly packaged DNA
Chromosomes take shape…
before division
Centromere
Connects the sides of chromosomes and are found in the pinched region of the chromosome
made of DNA and proteins
it connects the chromosome
Chromatin
DNA molecules and structural proteins combined
Seen in non-dividing cells
It is unwound DNA and proteins together - DNA does its work in this less compacted form
Histones
Proteins that the double helix wraps around (histones = proteins) when DNA replicates for organization
What form does DNA take during division?
Chromosome
What form does DNA take when not dividing?
Chromatin
The genome is distributed in ___
chromosomes (it is through chromosomes that our genetic information is distributed)
Genes are linear along ___
chromosomes
Humans have __ chromosomes arranged in pairs
46
Each chromosome contains..
1 continuous linear DNA helix
Haploid
A complete set of one of each chromosomes (23 total)
Diploid
A cell containing 2 sets of the 23 chromosomes in pairs (46 total)
Autosomes
22 chromosome pairs that do not determine gender
Sex Chromosomes
X and Y chromosomes
Female Sex Chromosomes
XX
Male Sex Chromosomes
XY
Reproductive Cells
Ova and Sperm (each only have 1 chromosome from each parent making them haploid (23) cells)
DNA is the basis of life because of 3 qualities what are they?
- they hold information
- It can copy itself
- it changes
In a female, only what is active in controlling the expression of genetic traits?
one X chromosome
Karyotype
an organized arrangement of all the chromosomes within one cell during the M phase of mitosis
Paired and then arranged by number according to size and position of the centromere
What model did Watson and Crick (1953) suggest was the proper model of DNA replication?
Semiconservative model
Meselson-Stahl Experiment
experiment that verified the semiconservative model of DNA replication
Semiconservative Model of DNA replication
Describes the method by which DNA is replicated in all known cells
It states that replication has DNA replicate before cell division to make two copies each containing one of the original DNA strands and an entirely new copy strand
RNA
long single stranded molecule involved in the actual synthesis of cellular enzymes and proteins
RNA polymerase
enzyme in the nucleus that synthesizes RNA
What is the structure of RNA
single nucleotide chain and one complimentary copy of a DNA strand
What is different between RNA and DNA?
- RNA is single stranded but DNA is double helix
- Thymine is replaced with Uracil in RNA
- RNA has a RIBOSE instead of Deoxyribose sugar
RNA can act …
as an enzyme and speed up chemical reactions
RNA is a ___ copy of a DNA strand
complementary copy
3 Types of RNA
mRNA
tRNA
rRNA
mRNA
Messenger RNA - “The Template”
Contains the transcribed instructions for protein synthesis obtained from the DNA molecule and carrier them to the cytoplasm while leaving the nucleolus
Holds the information on the order of amino acids in a protein via Codon sequences of nucleotides
Codon
chain of 3 mRNA nucleotides that specify insertion of one of the twenty different amino acids
A sequence of 3 bases forming a fundamental triplet code for transmitting information for protein synthesis
tRNA
Transfer RNA - “The Transporter”
Delivers the appropriate amino acids to the ribosome, where they are incorporated into the protein being synthesized
What is unique about tRNA shape?
There are 20 different kinds, each corresponding to one of 20 amino acids, in order to bring the AA to the ribosomes
Also it is a cloverleaf shape and the smallest RNA
What is the smallest RNA type
tRNA
Where is the site of protein synthesis
Ribosomes
rRNA
Ribosomal RNA - “The Synthesizer”
Provides the machinery needed for protein synthesis
It provides the structural support for the growing protein
Where is rRNA synthesized?
in the nucleolus (unlike other RNA types) and transported to the endoplasmic reticulum
Function and Structure of mRNA
functions as a blueprint; it is a code for a single protein (or polypeptide chain)
it is single stranded
Structure and Function of tRNA
the translator, capable of reading the mRNA language and binding corresponding amino acid to a growing peptide chain
cloverleaf shape
Structure and Function of rRNA
the factory, an “enzyme” of sorts
it is a complex with proteins
The bridge between the gene and protein is?
RNA
Transcription
the process of making RNA from DNA
RNA copy of a DNA sequence
Translation
the process of making proteins from RNA (genetic code to protein code)
In eukaryotes, RNA must undergo what to become mRNA
processing
Protein Synthesis
the selective activation of a gene which results in the production of the appropriate protein
What things are required to meet in translation for protein synthesis?
mature mRNA
tRNA
molecules carrying AA
rRNA
ATP and GTP
Verious protein factors
Where does transcription occur?
cell nucleolus
How is transcription done?
Weak H bonds of DNA are broken so free RNA nucleotides can pair with exposed DNA counterparts (unzipping) on the meaningful DNA strand –> RNA polymerase recognized the beginning or start sequence of a gene –> RNA polymerase then attaches to the double stranded DNA and copies the meaningful strand into a single strand of RNA –> once at the stop signal, the enzyme leaves the gene and releases the RNA strand
The Genetic Code
universal language used by most living cells
Four (nitrogenous) bases make up the alphabet for this code and can be arranged in 64 possible combinations of 3s called codons
Each gene provides the genetic code for making…
one specific protein
61 codon combinations correspond to a specific AA, but 3 are…
stop codons
How many amino acids are used in protein synthesis?
only 20, so the code is redundant or degenerate
Synonyms
codons that specify the same amino acids
they usually have the first two bases the same, but the third base differs
Stop Code/Coedon
signals the end of a protein molecule
Amino acids are the …
building blocks of life (and proteins)
the genetic code can survive…
the many stages of cell division, cell renewal, and tissue growth
Translation
process of matching amino acieds to corresponding sets of 3 bases (codons) and linking them into a protein
How does translation occur?
RNA leaves the nucleus and attaches to the (small rRNA subunit) ribosome to begin (it contains the instructions for a particular protein) –> AAs are brought by tRNA and linked to make polypeptide chains –> Ribosomes read the 3 bases together to do the corresponding bases
If the mRNA codon is UCG, what will the tRNA bring to link?
AGC (complementary/pair to it)
What is the pathway to DNA directed protein synthesis?
DNA (nucleus) –> mRNA (Nucleus) –> tRNA (cytoplasm) –> rRNA (ribosome in cytoplasm) –> protein synthesis
The basic structure of a protein is …
an amino acid sequence
What are proteins responsible for?
The functional diversity of cells
Performs most biological functions
Has many regulatory processes take place
Can cause many disease processes to occur
Where most drug targets are found (here and at translation)
What determines a proteins function?
the AA sequence/chain
Example of a protein that does regulatory processes?
Dystrophin - structural protein - it functions to maintain muscle integrity, and a mutation in the gene coding for this protein can lead to the most commonly inherited myopathy, Duchenne Muscular Dystrophy
Cell Proliferation
process by which cells divide and reproduce
inherent adaptive mechanism for replacing body cells when old cells die or additional cells are needed
__% of body cells are replaced daily either via mitosis or meiosis
10%
2 Kinds of Cell Division
Mitosis
Meiosis
Gametes
ovum and sperm
haploid (1 set of chromosomes)
designed for sexual function
one kind of cell
Somatic cells
any body cell diploid (2 chromosome sets) and not gametes
How many kinds of cells are there
200+
What are the 3 main types of cells
- Well differentiated that are unable to divide or reproduce
- Parent (progenitor) cells that continue to divide and reproduce
- Undifferentiated stem cells that can be triggered to enter the cell cycle and produce large numbers of progenitor cells when needed
Cell differentiation
process in which proliferating cells are transformed into different and more specialized cell types
process occurs in orderly steps
What does cell differentiation result in ?
Fully differentiated adult cell with specific sets of structural, functional, and life expectancy characteristics
What is the exchange existing with cell differentiation?
Increased specialization is exchanged for loss of ability to develop different cell characteristics and different cell lines
Stem cell
Cell that remains incompletely differentiated throughout life
remains quiescent until cell replenishment is needed
one daughter cell retains characteristics of a stem cell while the other differentiated into a parent or progenitor cell with a limited potential for differentiation and proliferation
Fully differentiated cells can no longer…
undergo mitosis
The ultimate stem cell is
a fertilized ovum
Cell Cycle
interval between each cell division
steps of cell division
Phases of the Cell cycle
G1 (Gap 1) Phase –> S Phase –> G2 (Gap 2) Phase –> M Phase –> loops or G0 Phase
G1 Phase
first phase of mitosis
cell resumes synthesis of RNA, proteins, and carbohydrates are synthesized but DNA synthesis ceases
This is the “Post mitotic phase”
The most variable in duration
S Phase
10-20 hours long
DNA Synthesis occurs; gives rise to 2 separate sets of chromosomes (one for each daughter cell)
G2 Phase
2-10 hours long
Premitotic phase where DNA synthesis ceases; RNA and protein synthesis continue though
M Phase
Mitosis Phase taking 0.5 to 1 hour
Phase of cellular division or mitosis
G0 Phase
Variable in length
Resting phase - phase in which cells are not actively dividing and are quiescent
What is the length of the cell cycle?
Can be anywhere from < 8 hours to > 1 year
The cell cycle phase longest in duration
G1 Phase
The cell cycle phase where chromosomes become dense enough to be visible and when Karyotyping can be prepared?
M Phase
Mitosis
Cell division of somatic cells
Asexual division
Occurs in M Phase
Involves DNA replication
Each daughter cell contains the same number of chromosomes as the parent cell
The 2 resulting daughter cells have identical sets of 23 chromosomes
Stages of Mitosis
“Interphase” –> Prophase –> Prometaphase –> Metaphase –> Anaphase –> Telophase –> 2 Diploid Cells
PPMAT !
Prophase
first stage of mitosis where the nuclear membrane breaks down and chromatin in the nucleus condenses into chromosomes
Prometaphase
second stage of mitosis where there is no longer a recognizable nucleus
Mitotic spindles elongate to specific areas on chromosomes
Metaphase
third stage of mitosis where tension is applied to spindle fibers which align chromosomes in one plane at the center of the cell
Anaphase
fourth stage of mitosis where chromosomes are pulled away from the central plane toward the cell poles
Telophase
fifth stage of mitosis where chromosomes arrive at cell poles and decondense
nuclear envelope re-forms around clusters at each end of the cell
Meiosis
cell division which occurs only in reproductive cells during the formation of gametes (sex cells)
How does DNA duplication differ in Meiosis compared to Mitosis?
A cell dividing by meiosis duplicates its DNA as with cells undergoing mitosis, BUT splits into 4 new cells instead of two and each contains only one copy of each chromosome - making them haploid
What is the benefit of meiosis?
Maintains the chromosome number while mixing gene combinations through crossover
Gametes form which cells?
Germ Line Cells
Crossing Over
a biological occurrence when paired chromosomes of the same type line up and recombine the genes
this process allows parental relation while still having the offspring have different copies from the parents and unique individual characteristics
Meiosis makes __ cells
4
Mitosis makes __ cells
2
Meiosis cells have ___ chromosomes
23 chromosomes
Mitosis cells have ___ chromosomes
46 chromosomes
Phases of Meiosis?
Interphase –> Meiosis 1 (PPMAT I) –> Meiosis 2 (PPMAT II) –> 4 Haploid Cells
Meiosis v Mitosis: DNA Synthesis
Meiosis - occurs in S phase of interphase
Mitosis: Occurs in S phase of interphase
Meiosis v Mitosis: Synapsis of Homologous Chromosomes
Meiosis - During prophase I
Mitosis - Does no occur in mitosis
Meiosis v Mitosis: Crossover
Meiosis: During prophase 1
Mitosis: Does not occur
Meiosis v Mitosis: Homologous Chromosomes line up at metaphase plate?
Meiosis: During metaphase I
Mitosis: does not occur in mitosis
Meiosis v Mitosis: Sister Chromatids Line Up At Metaphase Plate
Meiosis: During metaphase II
Mitosis: during metaphase
Meiosis v Mitosis: Outcome
Meiosis: 4 haploid cells at the end of meiosis II
Mitosis: 2 diploid cells at the end of mitosis
Interphase
phase when DNA replicates before cell division starts
2 Specialized forms of Meiosis
Oogenesis
Spermatogenesis
Oogenesis
Female sex cell meiosis to produce an ovum
Steps of Oogenesis
Meiosis I leads to a Secondary Oocyte and a Polar body –> Secondary Oocyte undergoes Meiosis 2 into an Ovum (mature oocyte) and a polar body, and the other polar body splits into 2 polar bodies
Result of Oogenesis
1 Mature Ovum
3 Polar Bodies
Polar Bodies
byproducts of oogenesis with no real biological role
Spermatogenesis
Male sex cell meiosis to produce 4 sperm
Steps of Spermatogenesis
Spermatogonium –Mitosis–> Meiosis I occurs leading to 2 secondary spermatocytes –> Meiosis 2 occurs leading to 4 viable daughter spermatids –> the 4 spermatids differentiate into sperm cells
What would happen if we did not have meiosis?
Sperm and Ovum would each get 46 chromosomes leading to a fusion of 92 chromosomes total
Human genome Project
1990-2003
Successful mapping of all genes in the human genome
Genome Mapping
project that shows the relative location of 2 genetic traits and often leads to the specific location of a gene locus
2 types of genomic maps?
- Genetic Maps
- Physical Maps
Linkage Studies
assume genes occur in a linear pattern in chromosomes, and identify inherited traits that occur at a greater rate together than they would be by chance alone
Linkage Analysis
can be used to clinically ID individuals in a family with a known genetic defect
Genetic Maps
use linkage studies to estimate distance between chromosomal landmarks
Physical Maps
measure the actual distance between chromosomal elements in biochemical units
How is hybridization studies used to visualize and map genetic material in a cell?
Isolation can be achieved by fusing the cell with a mouse/rat cell to make a hybrid cell
This hybrid cell can then be used to understand genetic mutations and chromosomal abnormalities
Hybridization studies are commonly used to study…
viruses and mutations involving cancer
Genotype
genetic information stored in base pairs
Phenotype
recognizable traits, physical or biochemical associated with a specific genotype
Homozygotes
persons in whom the two alleles of a given pair are the same (AA or aa)
Heterozygotes
persons having different alleles (Aa) at a gene locus
Recessive Trait
expressed only as a homozygous pairing (aa)
Dominant Trait
expressed either as homozygous (AA) or heterozygous (Aa)
Single Gene Trait
when only one pair of genes is involved in the transmission of information
follows mendelian laws of inheritance
Polygenic Inheritance
involves multiple genes at different loci with each gene adding a small additive effect in determining a trait
Predictable but with less reliability than single gene traits
Multifactorial Inheritance
similar to polygenic inheritance but also includes environmental effects on genes
Punnett Square
Shows potential genotypes and single gene inheritance expression for offspring of parents with TWO KNOWN GENOTYPES
Mendelian Genetics
refers to the rules of inheritance of a SINGLE GENE TRAIT (one where expression is determined by inputs of 2 alleles, one from each parent)
Does not apply to traits needing more than 1 gene (like polygenic)
Dominant Inheritance
required only one altered copy of a gene to result in gene expression
The child can have the trait as long as one parent has the trait
ex: Autosomal Dom - Huntington’s Coria Disease
Recessive Inheritance
inheritance requires two altered copies of a gene, one from each parent, to result in gene expression
ex: Autosomal Rec - Cystic Fibrosis
X Link Inheritance
Inheritance is associated with genes located on the X chromosome
How does X linked inheritance differ between men and women?
Men are hemizygous (XY) so a mutation on the X chromosome results in gene expression, but women need mutation/change in both X chromosomes to show full expression usually
Hemizygous usually related to mother passing the affected X chromosome to the son
Hemizygous
person with only one member of a chromosome pair or segment rather than the usual two
ex: XY in men
Autosomal Dominant Inheritance
Single Gene Trait
Controlling gene trait on an autosomal chromosome expresses regardless of homo or hetero zygosity
What kind of inheritance has carriers?
Recessive Inheritance
Risk for passing on dominant inheritance in a heterozygous, dominant homozygous, and recessive homozygous individuals?
50% for Aa
100% for AA
0% for aa
How does Dominant transmission stop?
when a generation arises where no family members are affected (have A)
Males and Females transmit Dominant traits…
with equal frequency
Males and female can be affected and transmission of male-male is possible
Does dominant traits skip generations?
no, successive generations are affected with no generations skipped
Autosomal recessive Inheritance
Single Gene trait
only expressed when homozygous for the recessive allele
male and females are affected and can transmit the trait
Do recessive traits skip generations?
They can because of carriers
usually then occurs in siblings rather than the parents
How many carriers do you need to pass on a recessive trait?
- just one creates a carrier potentially
If two parents are Aa, what are the chance of trait outcomes for the kids
AA - 25%
Aa (carriers) - 50%
aa (Affected with recessive -25%
How many X chromosome copies are needed for X linked inheritance in males?
only 1 (need 2 in girls)
How does affliction differ between males and females with x linked inherited disorders?
Females are affected less frequently and less severity if any, but can pass it on to their children
Why can men only pass their affliction onto their daughters and not their sons?
Because men contribute the Y chromosome to boys so they cannot move the X affliction on (but the mother still could if she is a carrier)
Example of an X linked recessive trait?
Red Green color blindness
Parents: X^BY and X^BX^b (25% normal male, 25% normal female, 25% female carrier, 25% color blind male)
Mutations
accidental errors in duplication of DNA
can occur in somatic or germ cells
usually acquired but may be inherited
What is the only way mutations can be inherited?
if the DNA is changed in the germ cell and passes on
Causes, Spontaneous or Environmental, for Mutations
substitution of one base pair for another
the loss or addition of one or more base pairs
rearrangement of base pairs
environmental agents
chemicals
radiation (80% of which is environmental)
Mutations can affect…
any part of the genome - transcription, proteins, translation, etc
How do the impacts of mutations vary?
No effect
Beneficial effect
Impairment
What sort of things can a harmful mutation cause?
Slow down protein synthesis
Impair protein function
Over Synthesize Proteins
Causes for Birth Defects
- Genetic Factors
- Environmental Factors (Fetal Development)
- Intrauterine Factors (rare)
Examples of Genetic Factors for Birth Defects?
single gene or multi factorial inheritance or chromosomal aberrations
Examples of Environmental Factors for Birth Defects?
maternal disease
infections
drugs taken during pregnancy
Examples of intrauterine Factors for Birth Defects?
fetal crowding
positioning
entanglement of fetal parts with the amnion
Characteristics of Single Gene Disorders
Caused by a single defective or mutant allele at a single gene locus
May be present on an autosome or X chromosome
May affect one member or both members of an autosomal pair
Defects follow the Mendelian patterns of inheritance
Characterized by their patterns of transmission which are obtained thru a family genetic history
How many generations need to be assessed for an accurate genetic family history?
3 generations
Autosomal Dominant Disorder
a single mutant allele from an affected parent is transmitted to an offspring regardless of sex
Autosomal Recessive Disorder
manifested only when both members of the gene pair are affected (both parents unaffected, but are carriers)
X Linked Recessive Disorders
Always associated with the X chromosome
inheritance pattern is predominantly recessive
Women need both X to be affected in this case
X Linked Dominant Disorders
conditions are expressed in both males and females, but are more severe in males
Mutant X supersedes other X for women in this case and causes the issue
You either have the mutant or not, if you do not then you cannot pass a mutant on unlike recessive
Examples of Autosomal Dominant Disorders
Marfan’s Syndrome
Neurofibromatosis (NF)
Marfan’s Syndrome
Autosomal dom Disorder
a connective tissue disorder manifested by changes in the skeleton, eyes, and cardiovascular system
Abnormality effects fibrillin 1 (coded for by FBN 1 gene)
No cure and diagnosis has major and minor criteria
Treatment is just regular system assessments for those at risk since it affects several organ systems
Neurofibromatosis (NF)
Autosomal dom disorder
Condition involving neurogenic tumors that arise from Schwann cells and other elements of the peripheral nervous system
Children with this are susceptible for neuro complications including increased incidence of learning disabilities, ADD, speech anomalies, and complex partial tonic clonic seizures
Examples of Autosomal recessive Disorders
Phenylketonuria (PKU)
Tay-Sachs Disease
Phenylketonuria (PKU)
Autosomal Rec Disorder
A rare metabolic disorder caused by a deficiency of the liver enzyme phenylalanine hydroxylase
Insidious onset and difficult to assess
Need a special diet
If untreated there will be impaired speech, intellectual inability, and other neurodevelopmental impairments
Testing for PKU is mandatory and occurs 24-48 hours post-birth
Tay-Sachs Disease
Auto Rec Disorder
A variant of a class of lysosomal storage diseases known as GANGLIOSIDOSE
Ganglioside in the membranes of nervous tissue are deposited in the neurons of the CNS and retina because of a failure of lysosomal degradation
Failure to break down GM2 ganglioside of a cell membrane leads to this
Infants appear normal at birth, but by 6-10 months there is decreased responsiveness, progressive weakness, muscle flaccidity, and death by age 4-5
This one highlights the important of family genetic history
Examples of X Linked Recessive Disorders
Red green color blindness
Hemophilia A
red green color blindness
X linked Rec Disorder
a person cannot distinguish between shades of red and green
So, on the X chromosome a gene for red sensitive opsin is need one or several green opsin so the sequences are similar and overlap leading to a crossover error
visual acuity is normal
more in males than females
Hemophilia A
X Linked Rec Disorder
Blood cannot clot properly due to a deficiency in factor VIII
Abnormally heavy bleeding even from a small cut, easy bruising, and potential internal bleeding into the muscles and joints can occur
Accounts for most cases (1 in 4500) while Hemophilia B is 1in 20,000 live male births
1/3 cases of hemophilia A are believed to be…
new mutations in the family rather than inherited from the mother
What may be used to check for hemophilia A pre-birth?
Perinatal testing checking for bleeding from the umbilical cord
How may women carriers differ in Hemophilia A presentation than men?
The carriers may show some mild signs of Factor VIII deficiency like easy bruising or taking longer to stop bleeding, but not all women show s/s just because they are carriers
Fragile X Syndrome
X Linked Disorder associated with a fragile site on the X chromosome where the chromatin fails to condense during mitosis
Affects more men than females (1 in 4000 rather than 1 in 6000) - but nearly 4x the amount of women are carriers
causes intellectual disability
in all ethnic groups and races
What is the second most common cause of Intellectual disability?
fragile x syndrome
FMR-1
Fragile site of the X chromosome
Fragile x syndrome is characterized when many CGC repeats occur here
mutations here are unusual compared to other genes
Nearly everyone with Fragile X syndrome have what?
instability in the gene leading to increased numbers of a portion of a gene in the CGC repeat region (50-200 CGC repeats)
Premutations
A mutation where the person does not have the disorder but are at risk for passing it on to children or grandchildren as well as a risk for adult onset disorders
What is the premutation in Fragile X syndrome
A CGC triplet repeat of 50-200 times
What adult onset disorder are Male carriers with the fragile X/CGC repeat premutation at risk for?
Fragile X Tremor Ataxia Syndrome (FXTAS)
What adult onset disorder are Female carriers with the fragile X/CGC repeat premutation at risk for?
Primary Ovarian Insufficiency (POI)
can cause premature menopause
FMR-1 Related Disorders
FXTAS
POI
How does full FMR-1 mutations differ between men and women?
All males with it will have Fragile x syndrome
However, some females with it will not have behavioral, cognitive, or physical features of Fragile x Syndrome
Is Fragile X Syndrome a Dominant or Recessive X Linked Disorder?
Both Yet Neither!!
Used to be thought mothers passed it on, but women express it differently when only have one problematic X chromosomes so it is hazy
Just know the disorder is from a fragile site
What are the characteristics of multi factorial inheritance disorders?
They are caused by multiple genes and environmental factors - but the exact number of genes is unknown
Do multi factorial inheritance disorders follow a pattern?
No they do not follow a clear cut pattern of inheritance
disorders can be expressed during fetal life and be present at birth, or expressed later in life
Examples of Multi Factorial inheritance Disorders
Cleft lip or palate
clubfoot
Congenital dislocation of the hip
congenital heart disease
pyloric stenosis
urinary tract malformation
Cleft Lip or Palate
multi factorial inheritance disorder
can vary from a small notch in the vermillion border of the upper lip to complete separation from the palate to the floor of the nose
Clubfoot
multi factorial inheritance disorder
internal rotation of foot around ankle
can be mild or severe
can be in one or both feet
Congenital Dislocation of the Hip
“Developmental Hip Dysplasia”
multi factorial inheritance disorder
hip joint does not form easily and the ball is loose in the socket allowing easy dislocation
Most often present at birth but can develop in the first year of life
Pyloric Stenosis
multi factorial inheritance disorder
thickening or swelling of the pylorus which causes severe forceful vomiting in the first few months of life
also called “Infantile Hypertrophic Pyloric Stenosis”
Chromosomal Disorders
Major category of genetic disease counting for a large proportion of early miscarriages, intellectual disabilities, and congenital malformations
Can be from abnormal numbers of chromosomes in autosomes or sex chromosomes, or it can be related to alteration in the structure of one or more chromosomes
What things can Chromosomal Disorders cause/manifest?
Reproductive Wastage
Congenital malformations
intellectual disability
*it is linked to 60+ identifiable syndromes present at birth
Reproductive Wastage
early gestational abortions
Types of Chromosomal Disorders
Structural Chromosome Abnormalities
Numeric Disorders involving Autosomes
Numeric Disorders involving Sex Chromosomes
Examples of Numeric Chromosomal Disorders involving Autosomes
Trisomy 21
Monosomy X
Polysomy X
Examples of Numeric Chromosomal Disorders involving Sex chromosomes
Turner Syndrome
Klinefelter Syndrome
Trisomy 21
Downs Syndrome
Extra/3 chromosomes on position 21 rather than 2
Can occur on the 13th and 18th chromosomes but 21 is the most common
Monosomy X
presence of only one member of a chromosome pair
mostly due to nondisjunction during meiosis
often leads to a spontaneous abortion when it is associated with autosomes
Polysomy X
more than 2 chromosomes in a cell
Turner Syndrome
Loss or partial loss of the X chromosome
Leads to early pregnancy loss with 99% not surviving first trimester
Usually only in girls as its missing an X chromosomes or part of a second X chromosome
S/S of Turner Syndrome
At Female Sexual maturity, there is no ovulation or menstruation that occurs
short stature
congenital heart disease
bicuspid aortic valve and/or alteration of aorta
short webbed neck
Klinefelter Syndrome
XXY karyotype - 47 - extra X chromosome
only in males
S/S of Klinefelter Syndrome
Manifests as a teen and young adult
testosterones drops and follicle stimulating hormone increases (FSH)
What is the most common chromosomal; abnormality?
turners syndrome
mtDNA only comes from…
the mother
All mtDNA disorders are inherited from…
the maternal line
mom can pass it to all children but only the daughters will pass the mutation to their children
Clinical expression of a Mitochondrial Gene Disorder depends on what?
total content of mitochondrial genes and the proportion that are mutant
How rare are mitochondrial diseases?
Very rare
as of September 2020 there were about 300 in existence
What are the manifestations and s/s of a Mitochondrial Gene Disorder?
It often affects more than 1 body organ system
muscle weakness
stroke like episodes and seizures
activity intolerance
myocardial myopathy
most syndromes have similar symptoms due to it impacting the neuromuscular system
Teratogenic Agents
Agents that produce abnormalities during embryonic or fetal development
It is a chemical, physical, or biological agent that produces these abnormalities
What are some examples of Teratogens?
Radiation
Chemicals and Drugs
Infectious Agents
Folic Acid Deficiency (showing how not just exposure, but nutritional deficiency counts too)
What are some example of chemical and drug teratogen exposure outcomes?
Fetal Alcohol Syndrome
Cocaine Babies
Folic Acid/Nutritional deficiencies
Prenatal smoking
How does sensitivity vary over time to teratogens?
different systems have different sensitivities at different times of development
When is the CNS most sensitive to teratogens?
About the first 2-4 weeks of development
When is the Heart most sensitive to teratogens?
About 2.5 to 6th week of development
When are the extremities most sensitive to teratogens?
about 3.5 to 7th week of development
when are the eyes most sensitive to teratogens?
about 3.5 to the 7.5 week of development
when is the external genitalia most sensitive to teratogens?
about the 6.5 to 8.5 week of development or so
What are the components of a genetic assessment?
Assessment of Genetic Risk and Prognosis
Detailed Family History
Pregnancy History
Detailed Accounts of Birth Process
Accounts of Postnatal Health and Development
Physical Examination of Affected Child and Family
Laboratory Testing
What are the 3 purposes of a prenatal diagnosis?
Information
Reassurance
Knowledge
How does a prenatal diagnosis lead to information?
Provides parents with information needed to make informed choices about having a child with an abnormality
How does a prenatal diagnosis lead to reassurance?
Provides reassurance and reduces anxiety among high risk groups
How does a prenatal diagnosis lead to knowledge?
allows parents at risk to begin pregnancy with assurance that knowledge about the presence or absence of a disorder can be confirmed with testing
Methods for Fetal Diagnosis
Maternal Blood Screening
Ultrasonography (non invasive allowing you to see soft tissue structures)
Obtaining Fetal Cells: Amniocentesis, Chronic Villus Sampling, Fetal Biopsy, Percutaneous Umbilical Fetal Blood Sampling
Cytogenic and Biochemical Analysis
When is maternal testing recommended?
Between 11 and 13 weeks
Amniocentesis
Invasive maternal testing for fetal diagnosis
can be done 13/14 to 20 weeks of pregnancy
Detects chromosomal abnormalities, neural tube defects, and genetic disorders
obtains fetal cells from the amniotic fluid via a needle
98-99% accurate but cannot determine severity of a birth defect
