Genetics Flashcards
DNA composition:
Double helix, nitrogen bases with deoxyribose-phosphate backbone
A- adenosine
C-cytosine
G-guanine
T-Thymine
RNA composition:
Single strand, nitrogen bases with ribose-phosphate backbone
A- adenine
C-cytosine
G- guanine
U- uracil
How is messenger RNA formed?
DNA transcribed–>
Primary mRNA–>
Splicing (introns removed)–>
Mature mRNA
What was ribosomal RNA do?
Part of the ribosome
Binds mRNA and tRNA to the ribosome
What does transfer RNA do?
Transports amino acids
Translates mature mRNA
Anticodon (at 3’ end) binds complementary mRNA codon
What is transcription?
Synthesis of an mRNA sequence from a DNA template
What is DNA polymerase?
Enzyme that utilizes complementary DNA strand as a template to create a new strand
What is RNA polymerase?
Enzyme that binds a promoter region to synthesize mRNA from the DNA template
What is reverse transcriptase?
Enzyme that transcribes RNA into DNA
A telomere is
The distal end of a chromosome that maintains integrity and stability
Mature mRNA is made from
Primary mRNA transcribed from DNA
The DNA segment between exons that is spliced out in mature mRNA
Intron
The DNA sequence transcribed to mature mRNA for ultimate gene material is
Exon
DNA transcription starts at
Promotor
Assembly of amino acids from mRNA and tRNA to protein is called
Translation
Identification of a DNA sequence by amplification then isolation of a specific sequence is
PCR
Southern analysis is
DNA identification with electrophoresis
Northern analysis is
Electrophoresis to identify RNA
Western analysis is
Electrophoresis to identify protein
FISH works by
Fluorescent tagging of a complementary DNA sequence with exposure to fluorescent light to identify presence or absence of that sequence
Ordered attachment of DNA molecular fragments to a slide is
Microarray
Can determine number of copies, over-/under- expression, or mutations in a gene
The most common malformations in the US are
Neural tube defects
Most malformations are due to
Unknown causes (70%)
Genetic causes of malformations are ___%
20%
Environmental causes ___% of malformations
10%
A mutation that results in a codon change to a stop codons is a
Nonsense mutation
A mutation that results in changing from one codon to another is
Missense mutation
A splice site mutation causes
Retained intron in mRNA, changing translation
A reciprocal translocation is
A break in 2 chromosomes with exchanged material, normal phenotype
A Robertsonian translocation is
Fusion of long chromosome arms with lost material from short arms
Normal phenotype until subsequent generations
X linked recessive inheritance pattern is
50% transmissible from female carrier as carrier to female offspring or as disease to male offspring
Universally transmitted carrier status to female offspring from male carrier with no transmission to male offspring
Potential abnormal phenotype in female carrier
X linked dominant inheritance pattern is
2x common in females
50% transmission to both male and female offspring from affected female
Universally transmitted disease to female offspring from male carrier with no transmission to male offspring
Common autosomal recessive disorders:
21-hydroxylase deficiency Cong muscular dystrophy Cystic fibrosis IEM (most) Sickle cell Thalassemia
Hematologic autosomal dominant diseases
Protein C and S deficiency
Spherocytosis
Gilbert
vWD
Neurologic autosomal dominant diseases
Congenital myotonic dystrophy
Neurofibromatosis
Genetic autosomal dominant diseases
Apert Crouzon Holt-Oram Marfan Noonan Stickler Treacher-Collins
Derm autosomal dominant diseases
Aplasia cutis Bullous ichthyosis Ichthyosis vulgaris Epidermolysis bullosa simplex Keratosis pilaris Partial albinism Peutz-Jegher Waardenburg
Renal autosomal dominant diseases
Adult PCKD
GI autosomal dominant diseases
Familial polyposis
Gardner
Alagille
Ophtho autosomal dominant diseases
Retinoblastoma
Ortho autosomal dominant diseases
Achondroplasia
Postaxial polydactyly
Osteogenesis imperfecta
Thanataphoric dysplasia
X-linked recessive metabolic disease
Fabry
Hunter
Menkes
Ornithine carbamyl transferase
X-linked recessive hematologic disease
G6PD
Wiskott-Aldrich
Hemophilia A and B
X-linked recessive neurologic disease
Color blindness
Duchene muscular dystrophy
X-linked recessive derm disease
Hypohidrotic ectodermal dysplasia
X-linked ichthyosis
X-linked recessive renal disease
Nephrogenic DI
Genomic imprinting is
Phenotypic variation based on maternal or paternal inheritance
Imprinting= silencing/deletion of that parent’s gene
Uniparental disomy is
Inheritance of both copies of a given gene from one parent
Trinicleotide repeat expansion
Increase phenotypic severity with each generations due to increased CTG repeat numbers
Recurrence risk of CHD
3%
Recurrence risk of cleft lip/palate
5-10%
Recurrence risk of hip dysplasia
3%
Recurrence risk of club foot
4%
Recurrence risk of Hirschsprung
4%
Recurrence risk of NTD
4%
Recurrence risk of pyloric stenosis
3% to subsequent sibling
Maternal inheritance: 19% in son, 7% in daughter
Paternal inheritance: 5% in son, 3% in daughter
Recurrence risk of Tri21
1% sibling risk in affected parents
5-10% with parental balanced translocation
Campylodactyly, thick lips, deep eyes, cupped ears with fetal demise in non-mosaic fetuses is
Trisomy 8
Cutis aplasia, midline defects, hyperconvex fingernails, clefts, and holoprosencephaly describes
Trisomy 13
___% of infants trisomy 13 sure within the first year
90%
95% of all cases result in SAB
VSD, clenched hands, rocker bottom feet, micrognathia, small mouth, female>male is
Trisomy 18
Prognosis of trisomy 18 is
95% SAB
90% death in the first year
Cri du chat is inherited _______ and presents with
Paternal, short arm 5th chromosome partial deletion
VSD hypertelorism Cat like cry Microcephaly Hypotonia FTT
Retinoblastoma, thumb hypoplasia, colobomas, microcephaly, cryptorchidism and SGA are consistent with
Deletion 13q
A maternal deletion of 15q11-13 with paternal uniparental disomy causes
Angelman syndrome
Presentation of Angelman syndrome is
Inappropriate laughter, large mouth, maxillary hypoplasia, puppet-like movement and gait, severe developmental delays with absent speech
Velocardiofacial syndrome is also _____ which is caused by _____
DiGeorge, autosomal dominant/de novo
22q11.2 deletion
DiGeorge presentation is noted by CATCH 22:
Cardiac Abnormal facies Thymic hypoplasia Cleft Hypocalcemia
4th brachial arch and 3/4th pharyngeal pouch defects
A deletion or methylation of 15q11-13 of paternal origin, maternal parental disomy results in
Prader-Willi
Rubenstein -Taybi syndrome is due to
Microdeletion of 16p13.3
Hypoplastic maxilla
WAGR represents
Wilms Tumor
Aniridia
GU abnormalities
Retardation
11p13 deletion
______ syndrome caused by 7q11.23 deletion presents with
Williams
Supravalvular subaortic stenosis Hypoplastic nails Prominent lips Stellate iris Mental deficiency
A mutation in the transmembrane domain of the fibroblast growth factor receptor 3 gene causes
Achondroplasia (4p16.3)
Autosomal dominant
Crouzon and Apert syndromes are both caused by
Autosomal dominant inheritance of mutation in fibroblast growth factor receptor 2 gene.
Unlike Apert syndrome, Crouzon presents with
Maxillary hypoplasia (not midface) Frontal bossing Premature mixed craniosynostosis Hearing and visual deficits Normal mental function
Risk of ________ malignancy in Beckwith-Wiedemann is ___% and is inherited _____
Wilms Tumor/hepatoblastoma
5-10%
Autosomal dominant, 11p15.5
ASD, absent or abnormal thumbs, and hypertelorism are consistent with
Holt -Oram syndrome
Autosomal dominant
An abnormal fibrin gene, inherited ______, causes ______
Autosomal dominant
Marfan syndrome
In contrast to Turner, Noonan is inherited ______ and has ___________ (signs).
Autosomal dominant
Dysplastic pulmonary valve Cryptorchidism Abnormal coagulation Increased von willebrands Cystic hygromas
The most mild form of osteogenesis imperfecta is
Type 4
Normal sclera
+/- abnormal dentition
The most severe type of osteogenesis imperfecta is ______ and causes
Type 2
Blue sclera
Short, broad bones
Stillbirth or early death
Osteogenesis imperfecta associated with easy bruising is type _____ and also has
Type 1
8-25% fractures at birth or in first year
Deafness
Wormian bones
Fractures present at birth is usually osteogenesis imperfecta ______ which also has:
Type 3
Blue sclera Macrocephaly Deafness Kyphoscoliosis Short stature
Osteogenesis imperfecta is inherited
Autosomal dominant,
Type 1 collagen defect
A type 2 collagen defect with autosomal dominant inheritance
Stickler syndrome
Myopia, spondyloepiphyseal dysplasia and flat facies are consistent with
Stickler syndrome
A mutation in the extracellular or intracellular tyrosine kinase domain of fibroblast growth factor receptor 3 gene is
Thanataphoric dysplasia
4p16.3
TCOF gene mutation causing 1/2nd branchial arch maldevelopment causes
Treacher-collins
‘mandibulofacial dysostosis’
Coloboma, mandibular hypoplasia, malar hypoplasia, hearing and visual deficits and hypoplastic zygomatic arch are
Treacher-Collins
Pigmentary abnormalities that can include deafness, Hirschsprung,
Waardenburg
Autosomal dominant, PAX3 or microphthalmia gene
Carpenter syndrome is ____ inheritance and has
Autosomal recessive
PDA, VSD
polydactyly
Dysmorphic facies
Brachycephaly
CHD in Ellis van Creveld is
Single atrium/ASD
Hyperpigmentation, radial and thumb hypoplasia, pancytopenia with increased risk of AML is
Fanconi pancytopenia syndrome
35% mortality
An autosomal recessive syndrome with ASD, polydactyly, occipital encephalocele and cystic dysplastic kidneys is
Meckel-Gruber
An autosomal recessive defect in cholesterol synthesis that causes increased 7-dehydrocholesterol is
Smith Lemli Opitz
Features of Smith Lemli Opitz include
Genital hypoplasia (under virilization)
Syndactyly
Mental deficiency
High mortality
Thrombocytopenia, absent radii and ulnar abnormalities is inherited _______ and has _____(CHD) and ____% mortality
Autosomal recessive
TOF
40% mortality from hemorrhage
CDH and Dandy Walker is
Fryns syndrome
Autosomal recessive
Inheritance of fragile X syndrome is
X-linked dominant with variable penetrance-
80% in males
30% in females
CGG repeats
Presentation of fragile X is
Long facies Prominent forehead Large ears Large testes Mental deficiency Hyperextensibility Autism
Kinky hair syndrome is
Menkes syndrome
X-linked recessive
Abnormal copper transport, inability to act as cofactor for enzymes
Infants who die early in infancy following twisted, lightly pigmented hair, cerebral deterioration, seizures, and wormian bones is
Menkes syndrome
Presentation of mitral valve prolapse, hypogonadism, gynecomastia, long limbs, behaviorism concerns is concerning for
Klinefelter
47 XXY
An infant with bicuspid aortic valve, CoA, cystic hygroma, webbed neck, gonadal dysgenesis, horseshoe kidney, short stature and broad chest likely has
Turner syndrome
45, XO
Outcome of most pregnancies with a fetus with Turner’s is
Spontaneous abortion (98%)
22q11 quadruplicate or triplicate results in
Cat eye syndrome
Major features of cat eye syndrome are
TAPVR
down slanting eyes Anal atresia Coloboma Mental deficiency Renal agenesis
Genetic cause of 6th and 7th nerve palsy is
Mobius sequence
Neurological defects in Mobius sequence can include ______. _______ _______ ________ and are associated with _____ and ______ syndromes
Brain nuclei destruction
Brain nuclei hypoplasia/absence
Peripheral nerve involvement
Myopathy
Poland and Klippel-Feil syndromes
An expressionless face, micrognathia, extensive cranial nerve dysfunction and limb deformities are consistent with
Mobius sequence
Micrognathia secondary to mandibular hypoplasia with hearing loss is
Pierre-Robin sequence
Pierre-Robin sequence can be associated with
Trisomy 18
Stickler syndrome
Treacher-collins
FAS
CHARGE association is
Coloboma Heart disease (TOF, DORV) Atresia of choana Restricted growth Genital hypoplasia Ear anomalies
Mental deficiency common (94%)
Micromelia, synophrys, thin down turned lip, long curly eyelashes, hypertonicity, microbrachycephaly, hirsutism, VSD suggests
Cornelius de Lange
Oculo-auriculo-vertebral or facio-auriculo-vertebral spectrum is also known as ______ and inherited
Goldenhar syndrome- 1st/2nd branch abnormalities
Sporadic
Goldenhar syndrome presents with
Malformed ears, pits or tags Hemivertebrae/hypoplasia Facial hypoplasia VSD Unilateral pattern
A sprengel deformity is part of
Klippel-Feil syndrome
- abnormal elevation and medial rotation of the scapula
A webbed neck with a short neck, low hairline, fused cervical vertebrae and deafness is
Klippel-Feil
Asymmetric limb hypertrophy with vascular lesions is
Klippel-Trenaunay-Weber
Proximal subclavian artery disruption causes
Poland sequence:
Poorly developed ipsilateral distal limb/pectoral region
Syndactyly
Male»
75% RIGHT
Small triangular facies, asymmetric skeleton, and a small incurved 5th finger is
Russell-Silver syndrome
Maternal uniparental disomy
VACTERL is
>3 of: Vertebral anomalies Anal atresia Cardiac (VSD) TEF Renal anomaly Limb dysplasia
Increased in IDM
