Chapter 6 Flashcards
What is the genome
An organisms genetic material
What is a Gene
Discrete set of nucleotides
A unit of inheritance
What is an Allele
A single gene locus
What is a Mutation
Permanent changes in DNA
What is a Hereditary mutation
A mutation to germ cells
What is a acquired mutation
A mutation to somatic cells
What is a point mutation
a single nucleotide is replaced by another and codes for an alternate AA
what is another name for a point mutation
missense mutation
What is a frameshift mutation
Insertion/deletion of 1 or 2 nucleotides (alters the reading frame)
What is a trinucleotide repeat
Amplification of a sequence of 3 nucleotides
What are single gene mutations also known as
Mendelian disorders
What are multifactorial inheritance mutations known as
Multigenic, or polygenic
What are the 4 categories of genetic disorders
Single gene mutations
Multifactorial inheritance
Chromosomal abnormalities
atypical inheritance
What category of mutations is the most rare
Single-gene mutations
What are the methods of inheritance
Autosomal dominant
Autosomal recessive
X-linked recessive
What is Pleiotropy
A single mutation may have a variety of phenotypic effects
What is genetic heterogeneity
Multiple mutations may be expressed as the same trait
What does it mean to have an autosomal dominant mutation
Only need one mutated gene to have disease
What do autosomal dominant mutations often affect
Structural proteins
Membrane receptros
What are the factors associated with autosomal dominant disorders
Reduced penetrance Variable expressivity (may or may not show phenotype)
What is the largest group of mendelian disorders?
Autosomal recessive
How many genes need to be mutated for a phenotype to show.
2
Is autosomal dominant or recessive associated with early onset/late onset
Dominant = Late Recessive = early
what type of autosomal disorder is associated with inbreeding
Autosomal recessive
What is a sex linked single gene mutation
X-linked disorders
What is the chance that the daughter and son have a bad X gene if mom has a bad X gene
50%
What is the chance that a daughter will get a mutated X if dad has a mutated X
100%
What type of single gene mutation is Marfan syndrome
Autosomal dominanat
What gene is mutated in marfan synrome
Fibrillin gene
What are some skeletal defects in marfan syndrom
Slender habitus Scoliosis Long limbs High arched palate Hypermobility
What potential fatal problem is associated with marfan syndrome
Ruptured aorta
What is the main problem with EHlers-Danlos syndrome
Defective collagen synthesis
What is characteristic of Ehlers-Danlos syndrome
Hyperextendsible skin
Hypermobile joints
What are problems associated with Ehlers-Danlos syndrome
Joint problems
poor healing
pneumothorax
What type single gene mutation is associated with Familial hypercholesterolemia
Autosomal dominant
What is the problem with Familial hypercholesterolemia
Impaired LDL transport + Catabolism
What increases the severity for Familial hypercholesterolemia
Whether the gene is Homozygous or heterozygous
What is associated with adult onset (heterozygous) of Familial hypercholesterolemia
Xanthomas (cholesterol deposit on tendon)
Premature atherosclerosis
What is associated with childhood (homozygous) onset of Familial hypercholesterolemia
Xanthomas
CAD (Lethal)
What type of single gene mutation is Cystic fibrosis
Autosomal recessive
What gene is mutated in cystic fibrosis
CFTR gene
Causes a decrease in chloride ion transport
What is cystic fibrosis associated with
Chronic pulmonary infections
Pancreatic insufficiency
Male infertility (absent vas deferens)
Very viscous mucus
What type of single gene mutation is Phenylketonuria (PKU)
Autosomal recessive
What is the main issue with PKU
can’t metabolize phenylalanine
it builds up and is a neurotoxin
What is associated with PKU
Mental retardation
Musty urine and sweat
Failed tyrosine production
What is the treatment for PKU
restrict phenyalanine
Supplement tyrosine
What is the issue with maternal PKU
Phenyalanine is teratogen (can cross placenta)
Causes problems with fetus
What type of single gene mutation is associated with Galactosemia
Autosomal recessive
What is the mutated gene in Galactosemia and what does it cause
Gene: GALT
Abnormal galactose metabolism
What happens to galactose in Galactosemia
galactose-1-phosphate accumulates
What happens when galactose-1-phosphate accumulates
it is toxic to CNE neurons, liver, lens of eye and kidneys
How long does an infant last that has Galactosemia?
no more than a few weeks
how do you treat an infant with galactosemia
Restrict galactose intake (from lactose)
What type of single gene mutation is associated with lysosomal storage disaeses
Autosomal recessive
What is a common problem with a lysosomal storage disease
There is a lack of lysosomal enzymes causing metabolites to accumulate and are stored within lysosomes
What are the 4 types of lysosomal storage diseases discussed in class
Tay-sachs disease Niemann-pick disease type A & B Niemann-pick disease type C Gaucher disease Mucopolysaccharidosis
What is the problem with Tay-sachs disease
The inability to metabolize Gm2 Gangliosides
What does tay-sachs disease cause
Mental retardation
Blindness
morot weakness
Death by age 2-3
What group is at a higher risk of tay-sachs disease
Ashkenazi jews
What is the problem with Niemann-pick disease type A and B
Accumulation of sphingomyelin in the liver, neurons, spleen, marrow, lymph nodes and lungs
What is different about Niemann-pick disease type C
Defective lipid transport
What type of niemann-pick disease is most severe
Type A (death by 3 years)
What type of niemann-pick is most common
Type C
What type of niemann-pick disease causes no neuo damage
Type B
What are the features of Niemann-pick type C
Childhood onset Ataxia Dystonia Dysarthria Variable prognosis
What is mutated in Gaucher disease
Glucocerebrosidase gene
What happens in gaucher disease
Glucocerebroside accumulates causing an enlargment of phagocytes
how many types of Gaucher disease is there
3
what is the most common type of gaucher disease
Type 1
What group of people is type 1 gaucher disease most common in
Ashkenazi jews
How do you treat gaucher disease
Enzyme replacement therapy
What is the main problem with Mucopolysaccharidosis
There is a deficiency in ECM breakdown enzymes
What happens to mucopolysaccharides in mucopolysaccharidosis?
Mucopolysaccharides accumulate in lysosomes
What skeletal deformation is strongly associated with mucopolysaccharidosis
Gargoylism
What are the two types of mucopolysaccharidosis discussed in class
Hurler syndrome (type 1) Hunter syndrome (type 2)
What type of single gene mutation causes Hurler syndrome
Autosomal recessive
What type of single gene mutation causes Hunter syndrome
X-linked
What type of mucopolysaccharidosis is associated with corneal clouding, skeletal abnormalities, mental retardation
Hurler syndrome
What type of mucopolysaccharidosis is mild, has no corneal clouding and is slow to progress
Hunter syndrome
What is Glycogenoses
Glycogen storage diseases
What type of single gene mutation is associated with Glycogen storage diseases
Autosomal recessive
What is the main issue with glycogen storage diseases
Impaired glycogen metabolism
What are the three glycogen storage diseases talked about in class
von Gierke disease (hepatic disease) McArdle disease (myopathic type) Pompe disease (type II glycogenosis)
What type of glycogen storage disease is associated with glucose-6-Phosphate deficiency
von Gierke disease (hepatic type)
What does von gierke disease cause
Hepatomegaly
Hypoglycemia
Death
What type of glycogen storage disease is associated with the live
von gierke disease
What glycogen storage disease is associated with muscle phosphorylase deficiency
McArdle disease
What glycogen storage disease causes a decrease in muscle glycolosis which leads to weakness/cramps
McArdle disease
What glycogen storage disease is associated with lysosomal acid maltase deficiency
Pompe disease
What organ in pompe disease found
Every organ
What can pompe disease cause in children
Lethal cardiomegaly
When does von gierke disease start to show
Neonatal
When does McArdle disease start to show
Young adult
What defines complex multigenic disorders
they have 2 or more altered genes causing an additive effect
What are the features of complex multigenic disorders
more altered genes = more risk
Identical twins share risk
First degree relatives have similar risk
Expression in first offspring, increase risk in siblings
What are cytogenic disorders
Altered chromosomes (structural, numerical)
What is the normal Haploid/diploid number in humans
Hap = 23 dip = 46
what are the different categories of cytogenic disorders
Loss of material
Gain of material
Sex chromosome abnormalities
Spontaneous alterations
What are the autosomal cytogenic disorders discussed in class
Trisomy 21
Trisomy 18
Trisomy 13
Cri du chat syndrome
What is the most common autosomal cytogenic disorder
Trisomy 21
What increases the risk of having a child that has trisomy 21
increase in maternal age
What are some features of trisomy 21
Flat faces Epicanthic folds cardiac malformations lung infections alzheimers atlanto-axial instability (30%)
What is the translocation that causes 4% of Trisomy 21
Robertsonian translocation (mom has 2 21’s but one is attached to another chromosome)
What is 22q11.2 deletion syndrome
Deletion of chromosome 22, long are, band 11.2
What does 22q11.2 deletion cause
Facial dysmorphism Cardiac defects cleft palate cognitive delays Hypoplasia
What are the two 22q11.2 diseases discussed in class
DiGeorge syndrome
Velocardiofacial syndrome
What chromosome do Allosomal cytogenetic disorders deal with
Chromosome 23: X, Y
What are the allosomal cytogenic disorders discussed in class
Klienfelter syndrome
Turner syndrome
What is chromosomally wrong in klinefelter syndrome
More than 2X, more than one Y
XXY
What causes klienfelter syndrome
Non disjunction during meisosis
What does klienfelter syndrome cause
Male hypogonadism + sterility Testicular atrophy Gynecomastia Really long legs Mild congitive impairment
What increases the risk of having a child with klienfelter syndrome
Increase in maternal age
irradiation
What chromosomal anomoly is associated with Turner syndrome
Absence of 1 x chromosome (45, X)
Or loss of short arm of X
What are the characteristics of Turner syndrome
Short stature
Amenorrhea (streak ovaries)
Neck webbing
Androgynous female appearance
What are hallmark examples of single gene disorders with atypical inheritance
Triplet-repeat mutations
Mutations in mitochondrial genes
Genomic imprinting (epigenetic silencing)
What type of atypical inheritance disorder is found in Fragile X syndrome
Triplet-repeat mutation (FMR1 mutation)
Repeats of CGG
What sex does fragile x syndrome affect
Males
What are characteristics associated with Fragile X syndrome
Familial Mental retardation Macroochildism Long face Large mandible Large ears flat feet hypotonia
What is unique with fragile X syndrome
As it gets passed down it gets progressively worse
What do mutated mitochondrial genes often cause
Defective oxidative phosphorylation
What disease is a hallmark of Mutations in mitochondrial genes
Leber hereditary Optic Neuropathy
What happens in Leber Hereditary Optic Neuropathy
Degeneration of retinal ganglia and CN 2
Causes loss of central vision
What two disease of genomic imprinting where discussed about in class
Angelman syndrome
Prader-wili syndrome
What is silenced in angelman syndrome
paternal imprinting and maternal deletion of 15q12
What is associated with angelman syndrome
Mental retardation
Seizures
ataxia
inappropriate laughter
What is silenced in Prader-wili syndrome
Maternal imprinting and paternal deletion of 15q12
What is associated with prader-wili syndrome
mental retardation hypotonia obesity short stature small hands/feet hypogonadism
What classifies pediatric diseases
Diseases that occur between birth to 17 years old
What is unique about childhood pathologies
May or may not be genetic origin
What are congenital anomalies
Structural defects present at birth
What are the two type of perinatal infections
Transcervical
Transplacental
What is characteristic of Transcervical perinatal infections
They ascends from vagina to cervix
What are some potential transcervical perinatal infections
Pneumonia
Meningitis
sepsis
Bacterial infections (strep, honorrhoeae, chlamydia)
What is characteristic of Transplacental perinatal infections
Hematogenous spread from compounds that cross the placenta (MC) or transfusion at birth
What is the acronym that is associated with Transplacental perinatal infections
TORCH
What is T.O.R.C.H
Toxoplasma gondii Rubella virus CMV HSV Other (HIV, HBV, syphilis)
What classifies a child as premature
less than 37 weeks gestations
What is the most common cause of neonatal mortality
Prematurity
What is a cause of Small-for-gestation-age (SGA)
Chromosomal disorders Fetal infection placental factors pre-exlampsia alcohol smoking maternal malnutrition
What is the gestational terminology for pre-term
less than 37 weeks
What is the gestational terminology for early term
37-38 weeks
What is the gestational terminology for full term
39-40 weeks
What is the gestational terminology for Late term
41 weeks
What is the gestational terminology for post-term
42 weeks
What causes Resptiratory distress syndrom in premature children
Immatur lungs, too little surfactant production
What does the first breath cause production of
Type II pneumocytes
What happens then there is not enough lung surfactant
difficulty inflating alveoli = atelectasis
What percentage of infants born
60%
What puts an infant at higher risk of RDS
maternal diabetes
males
cesarean section
pre mature birth
How is RDS treated
Steroids and Surfactant
Artificial ventilation
What happens in Necrotizing enterocolitis
Necrosis of intestine
ulcerations of intestine
congestion of intestine
abdominal distension
What is SIDS
sudden death of infant during sleep
When is SIDS most likely to happen
month 2-4
What are some risks of SIDS
Prone sleeping soft bedding bed co-sharing thermal stress maternal smoking being male
What caused a decrease of SIDS by 50%
the back to sleep campaign
What is Fetal hydrops
Accumulation of edema during gestation
What are the two types of Fetal hydrops
Hydrops fetalis
Cystic hygroma
Which form of cystic hydrops is lethal
Hydrops fetalis
What are some of the causes of Fetal hydrops
Immune hydrops: antibody induced
Nonimmue: chromosomal
What is the second most common death of 4-14 year olds
Pediatric tumors
What are the benign pediatric tumors discussed in class
Hemangioma
Lymphangiomas
sacrococcygeal teratomas
What pediatric tumor is of the capillaries, normally self resolves around age 7
Hemangioma
What is the benign pediatric tumor of the lymphatics of the neck, trunk and axilla
Lymphangiomas
What is the most common germ cell tumor of childhood
Sacrococcygeal teratoma
What percentage of sacrococcygeal teratoms are benign
75%
What are the most common tissues for pediatric malignancy
Hematopoietic
Neuronal
Soft tissue
How do pediatric malignancies differ from adult malignancies
Spontaneously regress
primative cell characteristcs
Teratogens, genetic abnormalities
What are 3 unique pediatric cancers
Neuroblastom
Retinoblastom
Wilms tumor
What type of tumor is a malignancy of neural crest-derived cells
Neuroblastoma
What pediatric malignant tumor encompasses 50% of infantile Cancer
Neuroblastoma
What age gives a better prognosis of neuroblastoma
younger than 18 months have the best prognosis
What is Homer-wright pseudo-rosettes
Neuroblastoma turmor cell that surrounds a neutrophil
What percentage of neuroblastoma are sporadic
98%
How do neuroblastomas metastasize
Lymphoid
hematopoietic
What is characteristic or infants with neuroblastoma that are less than 2 years old
Protuberant abdomen
Fever
cachexia
METS (blueberry muffin baby)
What Metastic tumor in infants is a cancer of the posterior retina
Retinoblastoma
What are the two types of retinoblastoms and their percentage of occurance
Genetic 40%
Sporadic 60%
What gene is mutated in retinoblastoma
RB1
What type of retinoblastoma is multiple and bilateral
Genetic
What type of retinoblastoma is isolated and unilateral tumor
Sporadic
How does a retinoblastoma appear on the retina
Nodular mass on the posterior retina
Flexner-wintersteiner rosettes
What is Flexner-Wintersteiner Rosettes
Cuboidal cells surrounding an empty lumen
What type of cancer is a wilms tumor
Renal cancer
nephroblastoma
What age is a wilms tumor most common
age 2-5 years
How does a wilms tumor appear as
A large palpable mass in the abdomen
What syndromes are associated with wilms tumor
WAGR syndrom
Denys-Drash syndrome
Beckwith-Wiedemann syndrome
What is WAGR syndrome
wilms tumor
Aniridia
Genitourinary
mental retardation
What is the treatment is Wilms tumor
Nephrectomy
Chemotherapy
What are prenatal indications for genetic ananlysis
any Increase risk of chromosomal abnormality
maternal age
prevoius chromosomal abnormalities
carrier of X-linked condition
How are prenatal genetics analysied
Amniocentesis
Umbilical cord blood
biopsy
What are postnatal indications for genetic analysis
Multiple convenital anomalies
Mental retardation
infertile offspring
How are postnatal genetics anaylsied
Peripheral blood lymphcytes
