Chapter 062. Principles of Human Genetics (Part 7) potx

It is estimated that transcription factors account for ~30% of expressed genes.. A growing number of identified genetic diseases involve transcription factors Table 62-2.. The MODY matur

Chapter 062 Principles of

Human Genetics

(Part 7)

Transcriptional Activation and Repression

Every gene is controlled uniquely, whether in its spatial or temporal pattern

of expression or in its response to extracellular signals It is estimated that transcription factors account for ~30% of expressed genes A growing number of identified genetic diseases involve transcription factors (Table 62-2) The MODY (maturity-onset diabetes of the young) disorders are representative of this group of diseases; mutations in several different islet cell–specific transcription factors cause various forms of MODY (Chap 338)

Table 62-2 Selected Examples of Diseases Caused by Mutations and Rearrangements in Transcription Factor Classes

Transcription

Factor Class

Example Associated Disorder

Complete or partial androgen insensitivity (recessive missense mutations)

Nuclear

receptors

Androgen receptor

Spinobulbar muscular atrophy (CAG repeat expansion)

Zinc finger

proteins

tumor, aniridia, genitourinary malformations, mental retardation

Basic

helix-loop-helix

MITF Waardenburg syndrome type

2A

mellitus type 4 (heterozygous mutation/haploinsufficiency)

Pancreatic agenesis (homozygous mutation)

Leucine zipper Retina

leucine zipper (NRL)

Autosomal dominant retinitis pigmentosa

High mobility

group (HMG) proteins

HNF1α, HNF1β

Maturity-onset of diabetes mellitus types 1, 3, 5

and 3

anomalies, atrial or ventricular septum defects, phocomelia)

Cell cycle

control proteins

P53 Li-Fraumeni syndrome, other

cancers

binding protein (CBP)

Rubinstein-Taybi syndrome

General

transcription factors

TATA-binding protein (TBP)

Spinocerebellar ataxia 17 (CAG expansion)

Von Hippel–Lindau syndrome

pheochromocytoma, pancreatic tumors, hemangioblastomas)

Transcription

elongation factor

VHL

inheritance, somatic inactivation of second allele (Knudson two-hit model)

Runt CBFA2 Familial thrombocytopenia

with propensity to acute myelogenous leukemia

Chimeric

proteins due to

translocations

PML—

RAR

Acute promyelocytic leukemiat(15;17)(q22;q11.2-q12) translocation

Note: Selected abbreviations include: SRY, sex determining region Y;

HNF, hepatocyte nuclear factor; CREB (cAMP responsive element binding) binding protein; VHL, Von Hippel–Lindau; PML, promyelocytic leukemia; RAR, retinoic acid receptor