Updated: 11/7/2018

Modes of Inheritance

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Pedigree Nomenclature

 pedigree

Autosomal Dominant (AD)
  • Genders affected
    • male and female at equal frequency
  • Generations affected
    • does not skip generations
      • if two parents without the AD disease have child with an AD disease
        • possibility is reduced penetrance
          • have mutant gene but phenotypically normal
        • de novo germline mutation
    • an affected child must receive disease from an affected parent
      • a homozygote dominant parent has a 100% of having an affected child
      • two heterotyzgote parents with the AD disease condition have a 75% chance of having a child with the disease phenotype 
  • Pathology
    • defects in structural genes
  • Presentation timing
    • usually after puberty
  • Other notes
    • often pleiotropic
      • several organ systems affected by single genetic defect
    • only one copy of the defective gene is required to express the disease phenotype
  • Examples
    • von Willebrand disease (most common)
    • Huntington's disease
    • osteogenesis imperfecta
    • achondroplasia
    • Marfan syndrome
    • neurofibromatosis type I
    • acute intermittent porphyria
Autosomal Recessive (AR)
  • Genders affected
    • male and female
  • Generations affected  
    • 1/4 of offspring affected when both parents are carriers
    • usually 1 generation
  • Pathology
    • defects in enzymes
  • Presentation timing
    • infancy to childhood
  • Other notes
    • most often more severe than AD
    • must have 2 defective copies of the gene
    • chances greatly increased with consanguinity
  • Examples
    • cystic fibrosis - deficiency in the chloride channel CFTR
    • inborn errors of metabolism
      • PKU, von Gierke's, Pompe's, glycogen storage diseases, sphingolipidoses (except Fabry's), and mucopolysaccharidoses (except Hunter's)
    • sickle cell anemia
    • thalassemias
    • albinism
    • ARPKD
    • hemochromatosis
X-linked Recessive (XR)
  • Genders affected
    • males must receive defective gene from carrier mother
      • carrier mother's sons have 50% of having disease 
    • affected males give copy to all of their daughters
  • Generations affected
    • skips generations
      • male-to-male transmission not allowed
      • diseases passes through carrier daughters
  • Pathology
    • defects in enzymatic genes
      • similar to AR diseases
  • Presentation timing
    • usually after puberty
  • Other notes
    • only one defective copy necessary for disease in males
      • because males are hemizygous for X chromosome
    • two defective copies necessary for disease in females
      • can be affected with just one defective copy if normal X chromosome is inactivated to Barr body
        • called manifesting heterozygotes
          • phenotype usually milder than affected males
  • Examples
    • hemophilia A and B 
    • Menke's disease 
    • Duchenne muscular dystrophy 
    • Lesch-Nyhan syndrome
    • Ornithine transcarbamoylase deficiency
    • red-green color blindness
X-linked Dominant (XD)
  • Genders affected
    • male and female at equal frequency
  • Generations affected
    • does not skip generations
      • only possibility is reduced penetrance
    • females of affected fathers are always affected
      • male-to-male transmission not seen
    • male or females of affected mothers can be affected
  • Pathology
    • defects in structural genes
  • Presentation timing
    • usually after puberty
  • Examples
    • hypophosphatemic rickets
    • Fragile X syndrome
    • Alport syndrome
Mitochondrial Inheritance 
  • Genders affected
    • male and females at equal frequency
  • Generations affected
    • does not skip generations
    • only transmitted from affected female 
      • gives to all offspring
      • due to the fact that the sperm do not contribute mitochondria to the zygote
  • Pathology
    • defects in electron transport/oxidative phosphorylation process
      • presents as neuropathies/myopathies 
        • neurons and muscle cells require high amounts of energy and depend on mitochondria
  • Presentation timing
    • usually after puberty
  • Other notes
    • variable expression due to heteroplasmy
      • a small percentage of mitochondria within a cell are affected leading to variable severity
  • Examples
    • myoclonic epilepsy with ragged red muscle fibers  
    • Leber hereditary optic neuropathy 
    • MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)
Inheritance Algorithm
  • Does offspring with disease have a parent with disease? (Y/N)
    • if YES
      • dominant (does not skip generations)
        • is there male-to-male transmission of disease? (Y/N)
          • if YES
            • autosomal dominant
          • if NO
            • do daughters of affected male have disease? (Y/N)
              • if YES
                • X-linked dominant
              • if NO
                • mitochondrial
    • if NO
      • recessive (can skip generations)
        • predominantly males with disease? (Y/N)
          • if YES
            • X-linked recessive
          • if NO
            • autosomal recessive
 

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Questions (18)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.BC.73) A 1-year-old boy with blonde hair, blue eyes, and fair skin is found to have mental retardation, eczema, and vomiting. A mousy body odor is apparent. Which of the following pedigrees best resembles the inheritance pattern of this disease? Review Topic

QID: 106554
FIGURES:
1

Figure A

24%

(43/177)

2

Figure B

50%

(89/177)

3

Figure C

8%

(15/177)

4

Figure D

10%

(17/177)

5

Figure E

3%

(6/177)

M1

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(M1.BC.27) The incidence of red-green color blindness in males in a certain population is 1/100. Which of the following is closest to the probability of a female and a male with normal vision having a daughter with red-green color blindness? Review Topic

QID: 107025
FIGURES:
1

1/100

17%

(2/12)

2

99/100

0%

(0/12)

3

1/50

8%

(1/12)

4

98/100

0%

(0/12)

5

0

75%

(9/12)

M1

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(M1.BC.73) A pregnant mother presents to your office with concerns regarding the risk that her fetus will suffer from an inherited disease. She reports a family history of hemophilia A in several of her relatives. Figure A shows a pedigree created after a thorough review of her family history (the mother in this scenario is represented by the arrow). This is her first child, and the father does not report any family history of blood disorders or other diseases. Which of the following is the probability that this patient's male offspring will have hemophilia A? Review Topic

QID: 106552
FIGURES:
1

0%

0%

(0/8)

2

25%

62%

(5/8)

3

50%

38%

(3/8)

4

67%

0%

(0/8)

5

75%

0%

(0/8)

M1

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PREFERRED RESPONSE 2
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(M1.BC.4708) An 11-year-old male is brought to his pediatrician for continuing management of a chronic lung infection. He has had many lung infections throughout childhood, and current sputum samples show oxidase positive, non-lactose fermenting gram-negative rods that produce a blue-green pigment. Physical exam shows nasal polyps and nail clubbing. He has also recently been experiencing floating foul smelling diarrhea, so he is prescribed enzymes and vitamin supplementation tablets. Which of the following chromosomes most likely contains the gene mutation responsible for this patient's symptoms? Review Topic

QID: 108475
1

7

61%

(61/100)

2

11

15%

(15/100)

3

17

8%

(8/100)

4

22

5%

(5/100)

5

X

7%

(7/100)

M1

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(M1.BC.1) A 19-year-old male presents to the university health clinic after a year of daily jerking in his limbs and experiencing a tonic clonic seizure witnessed by his roommate earlier today. He had been too embarrassed to come discuss his myoclonus, but he noticed that it had been increasing in frequency over the past few months. He noted that he tires very quickly when exercising, has poor vision and hearing, and was told that his mother, who passed away at his birth, also had similar symptoms. The physician sends for a muscle biopsy, which shows the following Gömöri trichrome stain (Figure A). What is the mode of inheritance of this disorder? Review Topic

QID: 106971
FIGURES:
1

Autosomal recessive

8%

(7/83)

2

Autosomal dominant

1%

(1/83)

3

X-linked dominant

11%

(9/83)

4

X-linked recessive

16%

(13/83)

5

Mitochondrial inheritance

63%

(52/83)

M1

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(M1.BC.0) A 5-year-old boy with a history of seizures presents to the pediatrician for several seizures occurring over the past month. The mother states that her son typically avoids recess, as he exhausts quite easily with any physical activity. He has also had headaches and vomits after he eats. A family history reveals that a maternal uncle and grandmother both had similar symptoms and both lost their vision and hearing by the age of 40. The mother explains that she also tires easily. With consent of the mother, a muscle biopsy was taken and a Gömöri trichrome stain was performed (Figure A). A blood analysis also revealed significantly elevated lactate levels. Which of the following statement best describes the mode of inheritance of the boy's disease? Review Topic

QID: 107004
FIGURES:
1

Females of affected fathers are always affected

0%

(0/21)

2

3/4 of the offspring are affected when both parents are affected and heterozygous for the diseased allele

19%

(4/21)

3

1/4 of the offspring are affected when both the parents are carriers

5%

(1/21)

4

Males are affected more often than females

14%

(3/21)

5

Transmission only occurs from females and may have variable expression

52%

(11/21)

M1

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(M1.BC.44) A 34-year-old male suffers from inherited hemophilia A. He and his wife have three unaffected daughters. What is the probability that the second daughter is a carrier of the disease? Review Topic

QID: 103407
1

0%

9%

(3/34)

2

25%

9%

(3/34)

3

50%

38%

(13/34)

4

75%

3%

(1/34)

5

100%

38%

(13/34)

M1

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(M1.BC.2) A 27-year-old G1P0 at 12 weeks gestation presents to her obstetrician for her first prenatal visit. She and her husband both have achondroplasia, and she is curious what are the chances that they will have a child of average height. What percent of pregnancies between two individuals with achondroplasia that result in a live birth will be expected to be offspring that are unaffected by this condition? Review Topic

QID: 102720
1

25%

29%

(63/216)

2

33%

36%

(78/216)

3

50%

12%

(25/216)

4

75%

8%

(18/216)

5

0%

14%

(30/216)

M1

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