Inheritance Patterns Flashcards
45,X describes what disease?
Turner Syndrome: Characteristic physical abnormalities, such as short stature, swelling, broad chest, low hairline, low-set ears, and webbed necks. Girls with Turner syndrome typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility. Concurrent health concerns are also frequently present, including congenital heart disease, hypothyroidism (reduced hormone secretion by the thyroid), diabetes, vision problems, hearing concerns, and many autoimmune diseases. Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas
47,XXY describes what disease?
Klinefelter Syndrome: Principal effects include hypogonadism and reduced fertility. A variety of other physical and behavioural differences and problems are common, though severity varies and many XXY boys have few detectable symptoms.
Familial polydactyly (having supernumerary fingers or toes) exhibits what type of inheritance?
Autosomal Dominant
Tuberous Sclerosis (a rare multi-system genetic disease that causes hamartomas to grow in the brain and on other vital organs) exhibits what type of inheritance?
Autosomal Dominant
Diagnosis of Tuberous Sclerosis (hamartomas in CNS and skin) can be complicated clinically by:
Variable Expression
Diagnosis of Tuberous Sclerosis (hamartomas in CNS and skin) can be complicated molecularly by:
Mosaicism (Somatic or Germline)
Neurofibromatosis 1 (A developmental syndrome caused by germline mutations in neurofibromin, a gene that is involved in the RAS pathway and causes tumors along the nervous system. NF-1 often comes with scoliosis (curvature of the spine), learning difficulties, eye problems, and epilepsy) exhibits what type of inheritance?
Autosomal Dominant
Marfan syndrome (a genetic disorder of the connective tissue. People with Marfan tend to be unusually tall, with long limbs and long, thin fingers) exhibits what type of inheritance?
Autosomal Dominant
Achondroplasia (a common cause of dwarfism) exhibits what type of inheritance?
Autosomal Dominant (It occurs as a sporadic mutation in approximately 75% of cases: associated with advanced paternal age)
Defects in what gene are responsible for Marfan Syndrome (a genetic disorder of the connective tissue)?
Fibrillin
Defects in the Fibrillin gene are associated with what disease?
Marfan Syndrome: A genetic disorder of the connective tissue. The most serious complications are defects of the heart valves and aorta. It may also affect the lungs, the eyes, the dural sac surrounding the spinal cord, the skeleton and the hard palate
Defects in the Fibrillin gene of what chromosome cause Marfan syndrome (a genetic disorder of the connective tissue)?
Chromosome 15q
Defects in what gene are responsible for Achondroplasia (a common cause of dwarfism)?
FGFR3
Defects in the FGFR3 gene are associated with what disease?
Achondroplasia: A common cause of dwarfism. The disorder itself is caused by a change in the DNA for fibroblast growth factor receptor 3 (FGFR3), which causes an abnormality of cartilage formation.
Defects in the FGFR3 gene of what chromosome cause Achondroplasia (a common cause of dwarfism)?
Chromosome 4p
What are some characteristics of Autosomal Dominant inheritance?
50% of offspring of affected individuals are affected. Equal numbers of males and females affected. Vertical transmission. Unaffected members of a family do not have affected children. Variable expression is common. Decreased penetrance is possible. Isolated cases likely due to new mutation
What are some characteristics of Autosomal Recessive inheritance?
Parents are asymptomatic carriers of the condition. 25% chance of recurrence in siblings. Equal number of males and females affected. Horizontal transmission. Consanguinity is possible, especially in very rare conditions
Cystic Fibrosis (abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions) exhibits what type of inheritance?
Autosomal Recessive
Thousands of deleterious mutations in the CFTR gene are associate with what disease?
Cystic Fibrosis: An autosomal recessive genetic disorder that affects most critically the lungs, and also the pancreas, liver, and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions
Mutations in what gene are associated with Cystic Fibrosis (abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions)?
CFTR
What is the most common mutation in Cystic Fibrosis (abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions)?
Delta-F508
Phenylketonuria (nonfunctional phenylalanine hydroxylase, the enzyme necessary to metabolize phenylalanine to tyrosine. Phenylalanine accumulates and is converted into phenylpyruvate, which is detected in the urine) exhibits what type of inheritance?
Autosomal Recessive
An error in the gene for what protein is associated with Phenylketonuria (phenylpyruvate detected in the urine)?
Phenylalanine hydroxylase (metabolizes phenylalanine to tyrosine
What are some characteristics of X-linked inheritance?
Incidence in males much higher than females. Heterozygous females may express the condition depending on pattern of X inactivation. Carrier females: 50% of sons affected, 50% of daughters are carriers. Affected males: all sons unaffected, all daughters are carriers (no male to male transmission). Affected males are typically related through females. Isolated cases usually due to new mutation
Duchenne Muscular Dystrophy (muscle degeneration and eventual death) exhibits what type of inheritance?
X-linked (recessive)
What disease is characterized by a mutation in the dystrophin gene?
Duchenne Muscular Dystrophy: The absence of dystrophin permits excess calcium to penetrate the sarcolemma. Water enters into the mitochondria which then burst. Mitochondrial dysfunction amplifies the stress-induced cytosolic calcium signals and an amplification of stress-induced reactive-oxygen species production. Increased oxidative stress within the cell damages the sarcolemma and eventually results in the death of the cell. Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue.
Duchenne Muscular dystrophy (muscle degeneration and eventual death) is characterized by a mutation in what gene?
Dystrophin: Dystrophin is responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal lamina (extracellular matrix) through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma. Water enters into the mitochondria which then burst. Mitochondrial dysfunction amplifies the stress-induced cytosolic calcium signals and an amplification of stress-induced reactive-oxygen species production.
Massively elevated Creatine Kinase levels at birth are common before the development of symptoms for what disease?
Duchenne Muscular Dystrophy: The absence of dystrophin permits excess calcium to penetrate the sarcolemma. Water enters into the mitochondria which then burst. Mitochondrial dysfunction amplifies the stress-induced cytosolic calcium signals and an amplification of stress-induced reactive-oxygen species production. Increased oxidative stress within the cell damages the sarcolemma and eventually results in the death of the cell. Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue.
The most common type of mental retardation in males results from what syndrome?
Fragile X Syndrome: The most widespread single-gene cause of autism and inherited cause of mental retardation among boys
What is the location of the fragile site in Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation)?
Xq27
Premutation alleles of Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation) commonly have what range of tandem repeats?
55-200 repeats
Premutation alleles of Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation) in men and women may develop into what disorder?
Fragile X-associated tremor/ataxia syndrome. FXTAS
What are the odds of men with premutation alleles of Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation) developing FXTAS after age 50?
1 in 3
Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation) is characterized by a mutation in what gene?
FMR1
Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation) is characterized by triplet repeat expansion. About how many repeats in the FMR1 gene?
>200 repeats
What is the “normal” amount of triplet repeats in an island of the genome?
Less than 40.
What is the main cause of mutation in the FMR1 gene that leads to Fragile X Syndrome (single-gene cause of autism and inherited cause of mental retardation)?
Triplet Repeat Expansions.
Myotonic Dystrophy (a chronic, slowly progressing, highly variable, inherited multisystemic disease characterized by wasting of the muscles, muscular dystrophy, cataracts, heart conduction defects, endocrine changes, and myotonia) demonstrates anticipation due to what type of disorder?
Triplet Repeat Expansions.
Many disorders caused by triplet repeat expansions show ________________?
Anticipation
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems) exhibits what type of inheritance?
Autosomal Dominant
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems) exhibits various onset. What are the approximate age of Adult onset HD?
About 40 years old
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems) exhibits various onset. What is the age for Juvenile HD? Is Juvenile HD severe?
Under 20 years old. YES, very severe.
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems) exhibits various onset. What is the approximate age for late onset HD? Is late onset HD severe?
Over 50 years old. NO, this is a milder form of disease.
Does the risk of Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems) decrease or increase with age?
Risk decreases as age increases.
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems): CAG triplet repeat in Exon 1 encodes for what?
Polyglutamine tract (a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units)
Does the polyglutamine tract or the CAG repeat cause Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems)?
Polyglutamine tract (a portion of a protein consisting of a sequence of several glutamine units. A tract typically consists of about 10 to a few hundred such units)
Huntington Disease (a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems): The CAG repeat is unstable in the male or female germline?
Male
What are the genes involved in Prader-Willi Syndrome (low muscle tone, short stature, incomplete sexual development, cognitive disabilities, problem behaviors, and a chronic feeling of hunger that can lead to excessive eating and life-threatening obesity)?
snoRNA genes
Are the maternal or paternal snoRNA genes usually imprinted?
Maternal.
If the maternal snoRNA genes are imprinted and the paternal snoRNA genes are normally expressed, how will one get Prader-Willi Syndrome (low muscle tone, short stature, incomplete sexual development, cognitive disabilities, problem behaviors, and a chronic feeling of hunger that can lead to excessive eating and life-threatening obesity)?
If the normally expressed paternal snoRNA genes are deleted.
What is the gene responsible for Angelman syndrome?
UBE3A
Are the maternal or paternal UBE3A genes usually imprinted?
Paternal.
If the paternal UBE3A genes are imprinted and the maternal UBE3A genes are normally expressed, how will one get Angelman Syndrome (a neuro-genetic disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky movements - especially hand-flapping, frequent laughter or smiling, and usually a happy demeanor)?
If the normally expressed maternal UBE3A genes are deleted.
Prader-Willi Syndrome (mental retardation, hyperphagia, obesity, hypogonadism, and hypotonia) and Angelman Syndrome (a neuro-genetic disorder) are associated with deletions in the genes of what chromosome?
Chromosome 15
Name 5 disorders associated with Uniparental Disomy.
- Prader-Willi Syndrome. 2. Angelman Syndrome. 3. Beckwith-Wiedemann Syndrome. 4. Silver-Russell Syndrome. 5. UPD14
Beckwith-Wiedemann Syndrome (an overgrowth disorder usually present at birth that is characterized by an increased risk of childhood cancer and certain congenital features) is associated with what chromosome?
11p15.5
Is paternal or maternal imprinting associated with Beckwith-Wiedemann Syndrome (an overgrowth disorder usually present at birth that is characterized by an increased risk of childhood cancer and certain congenital features)?
Paternal
What chromosome is affected in Silver-Russell Syndrome (one of the few forms of dwarfism that is considered treatable in some cases)?
UPD chromosome 7
UPD14 is usually the result of a Robertsonian translocation (a Robertsonian translocation joins the long arm of chromosome 21 with the long arm of chromosome 14 (or 15), the heterozygous carrier is phenotypically normal, however, the progeny of this carrier may inherit an unbalanced trisomy 21, causing Down Syndrome) inherited from the mother or father?
Father.
Williams Syndrome (a rare neurodevelopmental disorder characterized by a distinctive, “elfin” facial appearance, along with a low nasal bridge, an unusually cheerful demeanor and ease with strangers) is characterized by a microdeletion involving what gene?
Elastin gene.
A microdeletion in the elastin gene on the long arm of chromosome 7 causes what syndrome?
Williams Syndrome (a rare neurodevelopmental disorder characterized by a distinctive, “elfin” facial appearance, along with a low nasal bridge, an unusually cheerful demeanor and ease with strangers)
A deletion at 22q11.2 is associated with which syndromes?
Velocardiofacial Syndrome (palate, facial, and cardiac defects) and DiGeorge syndrome (thymic, parathyroid, and cardiac defects)
What is the chance of recurrence disorders caused by mitochondrial gene mutations in a woman?
100%
Achondroplasia
Autosomal-Dominant. FGF3, inc. paternal age
Polycystic Kidney Disease (adult)
Autosomal-Dominant. PKD1, chrom 16
Familial Adenomatous Polyposis
Autosomal-Dominant. APC gene, chrom 5
Familial Hypercholesterolemia (Type IIA)
Autosomal-Dominant. Defective/Absent LDL receptor
Hereditary Hemorrhagic Teleangiectasia
Autosomal-Dominant. arteriovenous malformations
Hereditary Spherocytosis
Autosomal-Dominant. Spectrin or Ankyrin defect
Huntington’s Disease
Autosomal-Dominant. CAG repeat, Chrom 4
Marfan’s Syndrome
Autosomal-Dominant. Fibrillin Gene
MEN
Autosomal-Dominant. 2A & 2B = Ret oncogene
NF1
Autosomal-Dominant. Chrom 17
NF2
Autosomal-Dominant. Chrom 22
Tuberous Sclerosis
Autosomal-Dominant. Skin & organ lesions, incomplete penetrance
VHL
Autosomal-Dominant. Deletion of Chrom 3p (hemangioblastomas and bilateral renal cell carcinoma)
Albinism
Auto-Recessive
Polycystic Kidney Disease (infant)
Auto-Recessive
Cystic Fibrosis
Auto-Recessive. CTFR Gene Chrom 7. Abnormal protein folding
Glycogen Storage Diseases
Auto-Recessive
Hemochromatosis
Auto-Recessive
PKU
Auto-Recessive
Sickle Cell Anemia
Auto-Recessive
Sphingolipidoses
Auto-Recessive
Thalassemias
Auto-Recessive
Bruton’s Agammaglobulinemia
X-linked Recessive
Wiskott-Aldrich Sydrome
X-linked Recessive. Progressive Deletion of B&T-cells. Thrombocytopenia, Purpura, Eczema, Infections
Fabry’s Disease
X-linked Recessive. The non-AR spingolipidosis. Alpha-galactosidase A defect. Accumulates Ceramide Trihexoside
G6PD Def
X-linked Recessive
Ocular Albinism
X-linked Recessive
Lesch-Nyhan Syndrome
X-linked Recessive. HGPRT
Duchenne/Becker’s Musculodystrophy
X-linked Recessive
Hunter’s Syndrome
X-linked Recessive. Lysosomal Storage Disease with no corneal clouding
Hemophilia A & B
X-linked Recessive. A - VIII. B - IX
Fragile X Syndrome
X-linked Recessive. FMR1 gene
Trisomy 18
Edward’s Syndome. micrognathia, low-set ears. low B-HCG
Trisomy 21
Down Syndrome. High B-HCG
Trisomy 13
Patau’s Syndrome. Cleft palate, polydactyly. Normal A-FP, B-HCG, Estriol
Cri-du-chat
Chrom 5 microdeletion. cat cry, VSD
Williams Syndrome
Chrom 7 microdeletion
DiGeorge Syndrome
22q11 deletion. (also Velocardiofacial syndrome)
Achondroplasia
Autosomal Dominant
Acute Intermittent Porphyria
Autosomal Dominant
Charcot-Marie-Tooth Disease
Autosomal Dominant
DiGeorge VCFS
Autosomal Dominant
Genetic Diabetes
Autosomal Dominant
Ehlers-Danlos Syndrome Type IV
Autosomal Dominant
Familial Hypercholesterolemia Type IIa
Autosomal Dominant
Huntington Disease
Autosomal Dominant
Marfan Syndrome
Autosomal Dominant
Osteogenesis Imperfecta Types I & IV
Autosomal Dominant
Von Willebrand Disorder
Autosomal Dominant
Thalassemias
Autosomal Recessive
Cystic Fibrosis
Autosomal Recessive
Cystinuria
Autosomal Recessive
Fanconi Anemia
Autosomal Recessive
Glycogen Storage Disorders
Autosomal Recessive
Lysosomal Storage Disorders
Autosomal Recessive
Osteogenesis Imperfecta Types II & III
Autosomal Recessive
PKU
Autosomal Recessive
Pyruvate Kinase Deficiency
Autosomal Recessive
Sickle-Cell Anemia
Autosomal Recessive
Duchenne Muscular Dystrophy
X-Linked Recessive
Fabry Disorder
X-Linked Recessive
Fragile X Syndrome
X-Linked Recessive
G6P Deficiency
X-Linked Recessive
Hemophilia
X-Linked Recessive
Lesch-Nyhan Syndrome
X-Linked Recessive
Red-Green Color Blindness
X-Linked Recessive
Mitochondrial Encephalopathy Lactic Acidosis Syndrome (MELAS)
Mitochondrial
Leber’s Hereditary Optic Neuropathy
Mitochondrial
Hairy Ears
Y-Linked
Recurrent Microdeletion Syndromes
Wolf-Hirschhorn, Cri-du-Chat, Wiliam-Beurer, Angelman, Prader-Willi, Miller-Dieker, Smikth-Magenis, DiGeorge VCFS
Gain of Function Syndrome
Charcot-Marie-Tooth Disease (AD) • Huntington Disease (AD) • Achondroplasia (AD) • Waardenburg Syndrome Type I (AD)
Diseases With Imprinting
Angelman/Prader Willi Syndrome, Beckwith-Wiedemann Syndrome, Silver-Russel Syndrome, Carotid Body Tumors, Pseudohypoparathyroidism, Transient Neonatal DM
Diseases with Anticipation
Huntington (AD), Myotonic Dystrophy (AD), Spinal Cerebellar Ataxia (AD), Friedreich Ataxia (AR), Fragile-X Syndrome (XLR)
