mendelian inheritance 2002 - michigan medicine · 2002-10-29 · mendelian inheritance 2002 •...
TRANSCRIPT
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MENDELIAN INHERITANCE2002
• Genotype• Phenotype• Locus• Allele• Homozygote/ Heterozygote• Compound heterozygote• Proband
A. ADB. ARC. XLRD. XLDE. Not genetic
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Mozart’s Piano Concerto in A-major is Köchel number
• A K365
• B K450
• C K482
• D K488
• E K491
Clinical vignette
• S G: 20 yo college student– Spontaneous rupture of the common iliac artery– Friable tissues, extensive bleeding– Past history:
• Easy bruising• Lax joints (fingers, elbows, left shoulder)
• D G: 53 yo mother of SG– Spontaneous perforation of the sigmoid colon– Past history
• Easy bruising• No joint laxity• Two normal pregnancies
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Laboratory analysis
• Skin fibroblasts: abnormal type III collagen
• COL3A1 DNA analysis: Gly25Val
• Diagnosis: Ehlers-Danlos Syndrome,
Type IV
Pedigree symbols
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Autosomal dominant inheritance
• Vertical
• Males and females affected
• Males and females transmit
• Each affected has one affected parent…
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NF1
Café-au-lait
Neurofibroma
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Lisch Nodules
Neurofibromatosis 1variable expressivity
• Café-au-lait spots
• Axillary freckling
• Lisch nodules
• Cutaneous neurofibromas
• Plexiform neurofibromas
• Scoliosis
• CNS tumors
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Marfan syndrome
Marfan ectopia lentis
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Marfan life expectancy
Marfan Syndromevariable
expressivity
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Incomplete penetrance
AD Erythermalgia
Achondroplasia
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What is the risk that this couple’schild will have achondroplasia ?
• A _
• B _
• C _
• D 1
• E 0
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Achondroplasiamutations in FGFR3
Allelic Heterogeneity
COL3A1 (EDS IV)
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Autosomal Recessive
Autosomal Recessive
• Horizontal
• Males and females affected
• Parents of affected are normal
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Autosomal recessive
A. ADB. ARC. XLRD. XLDE. Not genetic
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Locus Heterogeneity
IV-1,2,3,4,5,6 are all double heterozygotes
congenital deafness
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X-linked recessive
X-linked recessive inheritance
• “Diagonal”
• Males affected…
• Transmitted by carrier females
• NO male-to-male transmission
• Daughters of affected males are obligate carriers
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X-linkedrecessive
inheritance
X-linked dominant
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X-linked NOT sex-linked
Mitochondrial inheritance
• Mitochondrial DNA– 2 to 100 mitochondria/cell– 5 to 10 chromosomes/mitochondrium– 16.5 kb mt DNA– 37 genes
• Mitochondrial inheritance– Maternal– Heteroplasmy
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MERRF
MERRF Pedigree
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Heteroplasmy
Myotonic Muscular Dystrophy
• Most common inherited muscular dystrophy ofadults
• Muscle wasting—face, neck, distal muscles• Myotonia• Cardiac and smooth muscle affected• Cataracts• Immunoglobulin abnormalities• Insulin resistance• Occ. Mild MR
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Autosomal dominant
ANTICIPATION
DENIAL AIN’T JUST ARIVER IN EGYPT
-Rap song
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The absence of evidence is NOTequivalent to evidence of absence
Triplet (CTG) Repeats
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RepeatExpansion
Triplet Repeat Diseases
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Pathogenesis of MyotonicDystrophy
• Loss of Function– Haploinsufficiency of DMPK
– Cis-chromatin effects
Cis-chromatin effects
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Pathogenesis of MyotonicDystrophy
• Loss of Function– Haploinsufficiency of DMPK
– Cis-chromatin effects
• Gain of Function
Gain of Function
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Ypsilanti
Demetrius Ypsilanti
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Alexander Ypsilanti
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