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Flashcards in Exam 5: Birth Defects Deck (27)
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What are the five cellular processes that constitute development?

1) Transcriptional Regulation
2) Morphogen & Cell-to-Cell Signaling
3) Changes in cell shape and organization
4) Cell Migration
5) Programmed Cell Death


What are specific transcription factors in development?

- Specific transcription factors that only function in certain cells at certain times
- E.g. HOX


What are general transcription factors in development?

- Unspecific
- Found in thousands of transcriptional complexes
-E.g. CREBP & Rubenstein Taybi Syndrome


HOX Transcription Factors

- Falls under the general category of transcriptional regulation
- Specific transcription factor
- Important for patterning along the anterior-posterior axis/ limb development
- Mutation can lead to Synpolydactyly


Shh Morphogen

- Falls under the general category of morphogen/ Cell-Cell signaling
- Shh is secreted from the notochord/ neural tube and makes a morphogen gradient that organizes cells in the brain & spinal cord
- Mutations causes midline defects & development of posterior limb elements
- E.g. holoprosencephaly


Why does a defect in cholesterol biosynthesis affect development?

- Shh interacts with cholesterol
- Thus, disturbances in cholesterol biosynthesis have an effect on development through Shh
- Statins, cholesterol lowering drugs can have a detrimental effect as well


How does a cell change shape & polarity?

- Cells respond to their environment to change shape and polarity
- E.g. Polycystic kidney
- Developing kidney tubule must defect fluid flow to develop properly
- Mutation of Polycystin 1 & 2 make it incapable of sensing that flow
- Causes Polycystic Kidney Disease


How is cell migration necessary for development of the cerebral cortex?

- Neuronal stem cells have to migrate from the ventricular side of the neural tube along glial cells to their position int the cortex
- Mutation of LIS1 impairs this orderly process of migration
- Causes Lissencephaly (smooth brain)


What are the five processes that require programmed cell death?

1) Development of the heart
2) Separation of individual digits
3) Perforation of the anal and choanal membranes
4) Establishment of the connection between the uterus & vagina
5) Development of the immune system



Patient that truely has testes and ovaries (very uncommon)



Patients have testes or ovaries, but phenotype does not match or represent the genetic sex


How does the Y chromosome drive male development?

- We all start as females
- SRY, or Sex Determining Region of the Y chromosome is needed for
- TDF, testes determining factor that induces the androgens
- Androgens needed for the development of male external genitalia


Masculinization of female babies

- Congenital Adrenal Hyperplasia (CAH)
- Caused by a defect in 21-hydroxylase involved in cortisol biosynthesis
- No cortisol made, but intermediates are shunted into making androgens


Feminization of Male Babies

Problem with:

1) SRY (deletion or translocation)
2) TDF
3) Androgens (steroid 5a-reductase or androgen production/signaling impairment)



- Caused by Shh mutation
- Severely affected brain and face development (midline defect)


Smith-Lemli-Opitz Syndrome

- Impairment of Shh signaling secondary to a cholesterol biosynthesis defect
- Also called SLOS


Polycystic Kidney Disease

- Mutations is Polycystin 1 & 2
- Kidney is unable to sense fluid flow
- Differentiation does not STOP and the kidney develops numerous cysts



- Smooth brain/ cerebral cortex is thickened & lacks defined cell layers
- Causes severe mental retardation
- Caused by a mutation in the LIS1 gene, which impairs neuronal cell migration


Autoimmune Disease

- Lymphocyte lineage that reacts to self-components are supposed to be destroyed in development by apoptosis
- Failure of this process can result in autoimmune disease


Which HOX genes are involved in the development of the distal poles of limbs?

HOX 11-13



- Substance that is secreted by cells in one part of the embryo
- E.g. Shh


What are the phenotype & genotype if the SRY is deleted from the Y chromosome?

- Genotype= XY
- Phenotype= Female


What are the genotype & phenotype if the SRY is translocated to the X-chromosome?

- Genotype= XX
- Phenotype= Male


What is the most common cause of female pseudohermaphroditism?

- Congenital Adrenal Hyperplasia
- Defect in 21- Hydroxylase
- Cortisol NOT made, intermediates shunted into the production of androgens


What are the three common causes of male pseudohermaphroditsm?

1) Defect in testes development
2) Problem in androgen production by the testes i.e. a defect in steroid 5alpha-reductase
3) Androgen insensitivity syndrome i.e. a deficiency in androgen receptor production or signaling


Generally, what is the tumor progenitor model of cancer?

Errors in epigenetic programming of stem cells during development lays the seed for cancer later in life


How do errors in epigenetic programming lead to cancer?

- Abnormality in epigenetic programming of stem cells generates a pool of incompletely differentiated cells
- These cells retain some embryonal potential & may develop into a benign tumor
- Additional mutations in tumor suppressor genes/ oncogenes can lead to malignant transformation