Schizophrenia

Schizophrenia is a psychiatric disorder that causes a major derangement of personality marked by significant loss of perception of reality. Generally, schizophrenic symptoms begin during late adolescence, at about 19 to 21 years of age. An estimated 1 of the worldwide population has this debilitating condition. At any particular time, approximately 20 of hospital beds in the United States are occupied by schizophrenic patients. Patients with schizophrenia in its acute form cease to develop...

Clinical Management

Lustberg et al. (1970) presented evidence that ascorbic acid in high doses decreases binding of C(14)-homogentisic acid (HGA) in connective tissues of rats with experimental alkaptonuria. Long-term therapy in young patients with alkap-tonuria is indicated. Wolff et al. (1989) treated 2 adults and 3 infants with high doses of ascorbic acid and studied the effect on the excretion of homogentisic acid and its toxic oxidation product, ben-zoquinone acetic acid (BQA).The purpose was to determine...

Tdt

Genetic systems are inherently intricate. To date, much attention has been devoted to isolating and characterizing genes that have a major effect on a phenotype. Detailed analyses have shown that these monogenic traits are not simple genetically rather, both modifying genes and environmental (nongenetic) factors contribute to the final phenotype in many instances. As well, tools are now available to study traits that are determined by either a few or many genes. There are not many examples of...

Info

This regard, most of the current neonate tests rely on a sample of blood from the heel (heelstick), dorsal vein of the hand, or the umbilical cord. Because newborn tests are concerned with identifying the presence of a disorder and not primarily with the nature of the gene mutation(s) that causes the disorder, assays other than gene tests are often used. This approach is especially helpful if a disease is due to a number of different mutations within a gene that produce the same biochemical...

Abo A Abo Ab Abo A Abo B Abo B Abo O

And, of course, there is no possible way taking into account ethical, moral, and practical considerations that human matings can be controlled on the basis of the genotypes of the parents. Yet genetic analysis of human traits can be studied effectively from two perspectives. First, data from large populations can be collected and mathematical methods applied to deduce whether a particular trait is inherited. Although adequate, this approach requires the examination of many individuals, an...

Myoclonus Epilepsy and Ragged Red Fibers

Myclonus epilepsy and ragged red fibers (MERRF) is a rare, maternally inherited, heteroplasmic, debilitating multisystem disorder that includes transient seizures (myoclonus epilepsy), failure to coordinate muscle movement (ataxia), loss of muscle cells (myopathy), and, to a lesser extent, dementia, deafness, and degeneration of spinal nerves. The term ragged red fibers refers to large clumps of abnormal mitochondria that accumulate mostly in muscle cells and are stained red by a dye that is...

Skeletal Muscle Disorders Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked recessive, progressive muscle-wasting disease that affects approximately 1 in 3300 live-born males. DMD derives its name from French neurologist Guillaume Duchenne (1806-1875), who studied this devastating and ultimately lethal condition. The onset of DMD is evident at about 4 to 5 years, when affected children show muscular weakness of the hips, an inability to run, a characteristic set of maneuvers when rising from a kneeling position (Gower's...

Sdspage

Somatic cell In a multicellular eukaryotic organism, any cell that is not a germ line cell. somatic cell hybrid A cell line that maintains rodent chromosomes and one or a few human chromosomes. Also called cell hybrid, hybrid cell line. somatic cell hybrid panel A set of derived chromosome-specific hybrid cell lines, each carrying a different portion of a particular chromosome. The members of such a panel have chromosomal deletions and, in some cases, carry translocated chromosomes that retain...

Breast Cancer

In developed countries, approximately 2 of the women who live to 50 years and approximately 10 of those who survive to 80 years will experience the anguish of breast cancer. Despite early detection and improved treatments, many affected women will have breasts removed and about two-thirds will die within 10 years of diagnosis as a result of metastasis to the liver or other organs. Each year in the United States, about 180,000 new cases of breast cancer are diagnosed and 46,000 women die from...

Beckwith Wiedemann Syndrome

The major characteristic of the Beckwith-Wiedemann syndrome (BWS) is excessive fetal and postnatal growth. About 80 of BWS infants and children are greater than the 90th percentile for height and weight. After 6 years of age, overgrowth is not pronounced. Generally, the tongue is oversized. The abdominal body wall often fails to close at the base of the umbilical cord (omphalocele) because of enlarged internal organs (visceromegaly). Consequently, the intestines protrude from the body cavity at...

Transmission Disequilibrium Test

The transmission disequilibrium test (TDT) was originally developed to overcome the confounding effect of population stratification encountered with case-control association studies. The method effectively detects linkage with association. The key features of the TDT are tracking the transmission of alleles from heterozygous parents to affected offspring and determining whether the segregation is random or whether one allele is transmitted to an affected offspring more frequently than the other...

Parts of the Brain

Despite the frequency with which we hear the assertion that the brain is the most complex structure in the known universe, it remains a valid description of this extraordinary organ. The brain can be subdivided into six main regions the cerebrum, diencephalon, midbrain, pons, medulla, and cerebellum (Figure 14.5). The midbrain, pons, and medulla form the brain stem connecting the mass of the brain to the spinal cord. These three structures contain neurons that relay signals from the spinal cord...

Cataracts

Zonular Cataract Schematic

The lens of the eye is a biconvex transparent structure that refracts incoming light onto the retina (Figure 15.9). The central part of the lens is formed during embryonic development by elongating epithelial cells of the posterior lens vesicle and contains the lens primary nucleus. The front of the lens is covered with a thin layer of epithelial cells. Throughout life, newly formed fiber cells are produced from dividing epithelial cells just anterior to the central region (equator) of the...

The Logarithm of the Likelihood Ratio Method of Linkage Analysis LOD Score

In addition to the direct method of counting large numbers of recombinants and nonrecombinants to determine the recombination fraction between two loci in humans, a broader-based, indirect method was needed that (a) could rigorously distinguish between independent assortment and linkage, (b) was not necessarily dependent on knowledge of the actual phase of the doubly heterozygous parent, (c) could combine information from a number of different families, and (d) if linkage was evident, could...

Genotyping Single Nucleotide Polymorphisms

Polymorphic marker systems are necessary for genetic linkage and association (allele sharing) studies, determination of disease genes by linkage disequilibrium, and other applications, such as identifying the loss of alleles from a chromosome(s) in tumor cells. With the emergence of PCR and the discovery of the highly polymorphic nature of dinucleotide repeats, the firstgeneration polymorphic markers, restriction fragment length polymorphisms (RFLPs), were replaced by short tandem repeat...

Color Vision Defects

Human color vision is a complex phenomenon that depends on three types of cone photoreceptors, designated as red, green, and blue cones. In a normal retina, there are about 1.0 X 106 blue, 0.6 X 106 green, and 4.4 X 106 red cones. Each type of cone has a visual pigment (opsin, color pigment) that responds to light within a specific spectral range. The blue (short wavelength sensitive) opsin absorbs light maximally at about 426 nm, the green (middle wavelength sensitive) opsin at about 530 nm,...

Colorectal Cancer

Each year about 57,000 people in the United States die from complications caused by colorectal cancer (CRC) and approximately 147,000 new cases are diagnosed. Moreover, at least 1 in 2 people worldwide will develop a benign colorectal tumor by the age of 70. In 10 of these cases, malignancy will develop and the cancer will spread to other sites. Colorectal cancer need not be life threatening if it is detected early and the tumor(s) is removed surgically. The initial signs of CRC are blood in...

Radiation Hybrid Mapping

Radiation hybrid (RH) mapping does not require the assembly of pedigrees or family member genotyping. Instead, it depends on somatic cell techniques and on using PCR-based probes to screen a number of cell lines that carry various pieces (fragments) of human DNA. A monochromosomal hybrid or whole human genome cell line can be used for building radiation hybrid maps. The cells of the cell line (donor cells) are treated with a dose of ionizing radiation from X or gamma (g) rays that will kill the...

Regulation of the Cell Division Cycle

The cell division cycle requires a fine-tuned, temporal coordination of many sequential, diverse, and simultaneous events to ensure that, among other things, genomic DNA is precisely duplicated within a specified time period, DNA errors are repaired, chromosome compaction and the chromosome distribution process are precisely synchronized, and the splitting of a cell is not premature. Although much has been learned in the last 10 years about how the cell division cycle is controlled, there are...

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome), which affects about 1 in 200 individuals, is the most common inherited cancer syndrome. It behaves as an autosomal dominant trait. The phenotype is characterized by few colonic polyps (< 100) and early onset of multiple tumors in the Philadelphia Chromosome, Two-Hit Hypothesis, and Comparative Genomic Hybridization In the early 1970s, when chromosome banding was a newly developed technique, Janet Rowley (b.1925) demonstrated...

Contents

Eugenics Genetics Misinterpreted 9 The Molecularization of Genetics 11 OMIM An Important Online Source of Information About Human Genetic Disorders 14 Key Terms 17 Summary 17 References 18 Review Questions 18 Maintaining the Chromosome Number 19 Cell Division Cycle The Mitotic Process 20 Whole Chromosome Changes Aneuploidy 28 Determining the Phases of the Cell Cycle 32 Key Terms 35 Summary 35 References 36 Review Questions 36 The Genetic System Mendel's Laws of Inheritance and Genetic Linkage...

Dysgenics Fact or Fiction

Human population genetics tries to account for current allele and genotype frequencies in populations based on past circumstances, and to determine what these frequencies may be under various conditions in the future. Predictions of biological phenomena, especially those relating to humans, are at best precarious. However, notwithstanding the need for caution, there are some who are convinced that the human gene pool is deteriorating. The crux of the genetic decay (dysgenics) argument is that...

Neuronal Channelopathies

Channel proteins, in many cases, facilitate and regulate the flow of specific ions and small charged molecules in and out of a cell. The process of opening and closing (gating) of a channel is finely tuned. The channels that handle ions (ion channels) respond to the electric potential across the membrane (voltage gated) and other channels to signaling molecules (ligand-gated). The voltage-gated channels are part of an extensive family of more than 400 related proteins. The ion channels in...

Parentof Origin Effect

One of the tenets of Mendelian genetics is that reciprocal crosses with autosomal loci produce the same ratios and phenotypes among the offspring. For example, parents who are each homozygous for different autosomal alleles have only heterozygous offspring with the same phenotype regardless of the type of dominance Figure 11.1 . An indication of a non-Mendelian process is the consistent lack of phenotypic equivalence from reciprocal matings. Such a situation may arise when an allele from one...

Independent Assortment

In addition to conducting crosses with single gene pairs monogenic crosses , Mendel studied the simultaneous fates of two different traits determined by two gene pairs digenic crosses . He assumed that the two traits would either be transmitted independently of each other or would remain together from one generation to the next. For example, when true-breeding plants with round and yellow seeds RRYY were crossed with plants that only produced wrinkled and green seeds rryy , all the Fj plants...

Mitochondrial DNA Defects

A number of kindreds have been found with autosomal dominant inheritance of progressive external ophthalmoplegia adPEO . In these cases, the pheno-type also includes ptosis, skeletal muscle weakness, sudden death, and, to varying degrees, ataxia, deafness, and depression. Onset of the disorder frequently occurs within the fourth decade of life. Analysis of the mitochondrial DNA of affected individuals from these families indicated that large numbers of mitochondrial genomes have deletions of...

Plasmid Cloning Vector pUC19

The plasmid pUC19, which is maintained in the bacterium E. coll, is a generalpurpose vector often used for cloning DNA fragments up to about 8kb in length. This vector is well conceived and useful for illustrating the basic principles of vector-based cloning strategies. Generally, plasmid cloning vectors are denoted by a lowercase p, for plasmid, followed by an abbreviation that may be descriptive or anecdotal. The pUC19 vector is a circular double-stranded DNA molecule with 2686 bp containing...

Blue Cone Monochromacy

The loss of all red and green color vision blue cone monochromacy BCM X-linked incomplete achromatopsia blue cone monochromatism is a rare X-linked disorder affecting about one in 100,000 worldwide. A hallmark of BCM is the absence of both red and green cones, which, despite the presence of blue cones, abolishes all color discrimination and produces a colorless world. In addition, decreased visual acuity, nystagmus, and, in some individuals, progressive degeneration of the central retina are...

Oncogenes

The convergence of cytogenetics of human leukemias, studies of retrovirus-induced cancers in rodents and other animals, and recombinant DNA technology created a foundation for understanding the molecular basis of cancer. From the beginning of the twentieth century, researchers were aware that chromosome abnormalities were common in cancer cells. However, the cause-or-effect issue concerning these changes was controversial. Some argued that both loss of chromosomes and structural alterations...

Molecular Genetics of Red and Green Color Vision Defects

The genomic arrangements of the red and green opsin genes in men with color vision defects have been examined with Southern blot analysis and gene-specific PCR amplification. In general, these studies show that color vision abnormalities are most often the result of the formation of novel genes hybrid genes that contain sequences coding parts of the red and green opsin genes. Missense and nonsense mutations have rarely been associated with red or green color vision defects. Because of the high...

Review questions

If the guanine content of a genome is 24 , what are the proportions of the other nucleotides in the DNA of this organism 2. Discuss the basic features of DNA replication. 3. Compare and contrast DNA and RNA. 4. Describe the initiation of transcription of a eukaryotic gene. 5. What is a primary RNA transcript 6. Describe the initiation of translation in a eukaryotic organism. 7. Describe the elongation phase of translation. 8. Deduce the most likely DNA coding sequence for the following human...

Huntington Disease and Other Trinucleotide Repeat Expansion Diseases

Trinucleotide Repeat Expansion

Huntington disease HD is a catastrophic disorder affecting about 1 in 10,000 people worldwide. Its first signs usually begin at about 35 years of age, although onset can occur anytime during the human life span. In families with a history of HD, there is a marked tendency for the disorder to occur earlier and earlier in successive generations. Initially, muscle coordination is slightly impaired, and forgetfulness, cognitive disorganization, and personality changes are evident. These symptoms...

Human Visual System Structure of the

Figure Structure The Eye

The adult human eyeball is a nearly spherical structure, with a diameter of about one inch 25 mm . The globe has three layers in the posterior portion, and, of these, the outer and middle layers form specialized components of the anterior frontal structures of the eye Figure 15.1 . The outer supporting layer fibrous tunic has two contiguous components. An opaque, white, tough fibrous layer, called the sclera, covers the posterior five-sixths of the eyeball. The cornea, a transparent convex...

Structure of Skeletal Muscle

Skeletal muscles are composed of clusters of muscle cells, which are also called muscle fibers, myofibers, or myocytes. A muscle cell is long and spindle-shaped and contains many nuclei, that is, multinucleate. The plasma membrane cell membrane of a muscle cell is called the sarcolemma, and the cytoplasm is called the sarcoplasm. Some muscle cells can be gt 30 cm in length, whereas An Introduction to Human Molecular Genetics, Second Edition, by Jack J. Pasternak ISBN 0-471-47426-6 Copyright...

Rod Monochromacy

The total loss of color vision rod monochromacy RM rod monochroma-tism complete achromatopsia total color blindness is a rare autosomal recessive condition that affects about one person in 30,000. The retinal cones are either absent or defective. Accompanying features include nystagmus, impaired visual acuity, and extreme sensitivity to light photophobia . At least three RM genes have been characterized. Briefly, CNGA3 at 2q11.2 and CNGB3 at 8q21.3 encode the a and b subunits of the...

Dystrophin and Associated Muscle Proteins

A set of noncovalently associated proteins forms an interconnected system extending from the F-actin myofilaments and the cytoskeleton in the sar-coplasm to the matrix that surrounds each muscle cell Figure 13.3 . The N-terminal end of the muscle protein dystrophin is attached to F-actin, and the region near the C-terminus of dystrophin binds to 3-dystroglycan embedded in the sarcolemma. In addition, a-dystrobrevin, a sarcoplasm protein, binds to Figure 13.3 Schematic representation of the...