Non-Mendelian Inheritance - Lesson 3: Mosaicism


Cat
The colored patches in the calico cat are due to mosaicism (skewed X inactivation).

Click here to see an animation illustrating the development of mosaicism

3.1   Mosaicism



Embryo

3.1.1   Mutation



Cell Division

3.1.2   Mutation



Mutation early in tissue developement

3.1.3   Mutation



Calico cat

3.1.4   Mutation



A pedigree of germline mosaicism for an AD condition
A pedigree of germline mosaicism for an AD condition.

3.2   Germline Mosaicism



A radiograph of a premature infant with the perinatal lethal form of OI.
A radiograph of a premature infant with the perinatal lethal form of OI. Notice the skull is relatively large and unmineralized, the thoracic cavity is small, the long bones of arms and legs are short and deformed, and all the bones are not fully mineralized
(Reprinted from Thompson & Thompson Genetics in Medicine, 6th ed., Nussbaum RL, et al, ©2001, with permission from Elsevier Science.)

3.2.1   Osteogenesis Imperfecta

OI Type Disease Features

I

Mild bone fragility, normal stature, few bone deformities, blue sclerae, hearing loss in 50%, dentinogenesis imperfecta (abnormal dentin and opalescent blue-gray or yellow teeth) only in some cases

II

Extreme bone fragility, long bone deformities; lethal in perinatal period (most severe form)

III

Severe bone fragility, very short stature, variably blue sclerae, progressive bone deformities, dentinogenesis imperfecta common

IV

Bone fragility is variable, short stature, normal sclerae, mild to moderate bone deformities, hearing loss in some patients, dentinogenesis imperfecta common



3.2.2   Duchenne Muscular Dystrophy (DMD)



3.3   Somatic Mosaicism



A. an infant girl with Down syndrome. B. Same girl in A 7 years later
A, an infant girl with Down syndrome. Notice the typical facial features associated with this disorder: upslanting palpebral fissures, redundant skin of the upper eyelid (epicanthal fold), protruding tongue, and low nasal bridge. B, Same girl in A 7 years later. The typical facial features are still present, but they are not as pronounced.
(Reprinted from Medical Genetics, 2nd ed., Jorde LB, et al, ©2000, with permission from Elsevier Science.)

3.3.1   Down Syndrome (Trisomy 21)



café au lait spots
You can see the café au lait spots here which are the most useful diagnostic feature. The diagnostic criteria include having six or more café au lait spots at least 15mm in diameter, mainly located on the trunk
(Reprinted from Thompson & Thompson Genetics in Medicine, 6th ed., Nussbaum RL, et al, ©2001, with permission from Elsevier Science.)

3.3.2   Neurofibromatosis Type I (NFI)



3.3.3   Genetics and Cancer