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At least 19 recordsLinked to original sources
PubMed1992

A biochemical genetic study of alcohol dehydrogenase isozymes of the medfly, Ceratitis capitata Wied.

A concerted effort is under way to analyze, at the genetic, biochemical, and molecular level, the Adh gene system in the medfly Ceratitis capitata, an important agricultural pest. The isoelectric focusing (IEF) pattern of alcohol dehydrogenase (ADH) of the medfly demonstrates the presence of two well-differentiated, genetically independent dimeric proteins, called ADH-1 and ADH-2. These proteins do not exhibit interlocus heterodimeric isozymes, and the genes are not controlled coordinately during development, Adh1 and Adh2 being expressed mainly in muscle or in fat body and ovary, respectively. From the intensity of the IEF isozyme patterns, primary alcohols are judged to be better substrates than secondary alcohols, in contrast with Drosophila melanogaster ADH, and ethanol is probably the most efficient substrate for both sets of isozymes. The isoelectric points of ADH-1 (pI = 5.4) and ADH-2 (pI = 8.6) are different from D. melanogaster ADH (pI = 7.6), but the medfly ADH-1 has a native molecular weight (approx. 58 kD) close to that of D. melanogaster. A population survey of samples both from laboratory strains and from wild geographically different populations showed that the Adh1 locus is more polymorphic than Adh2. The most variable populations are from Africa, the supposed source area of the species. Further, a case of selection at the Adh1 locus under laboratory conditions is reported. The hypothesis of Adh gene duplication and the degree of similarity between medfly and Drosophila ADH are also discussed.

Alcohol Dehydrogenase↗
PubMed1974

Genetics of somatic mammalian cells: biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism.

Studies are presented on the biochemical genetics of 30 adenine-requiring mutants of the Chinese hamster ovary cell which were induced by mutagenesis and selected by the BrdU-visible light technique. Representative experiments conducted with these mutants include: hybridization with each other; hybridization with normal human cells; nutritional analysis; biochemical analysis with radioactively labeled intermediates; and measurement of reversion frequencies to wild-type phenotype occurring spontaneously and under the influence of selected mutagens. All mutants behave as if having point mutations. These experiments provide information relevant to the determination of dominant-recessive relationships, resolution into different complementation classes, localization of the human chromosomes which carry human genes required by the individual mutants, determination of the point of metabolic block for different mutants, and elucidation of the nature of the underlying DNA changes. These experiments illustrate the range of biochemical-genetic studies now possible with such a family of somatic mammalian cell mutants in vitro. Possible application to problems of human genetic disease are indicated.

Adenine↗
PubMed2001

Henry Friesen Award Lecture. Work, the clinician-scientist and human biochemical genetics.

The pursuit of human biochemical genetics has allowed us to understand better how the person with the (genetic) disease differs from the disease the person has and to develop the concept that genetics belongs in all aspects of health care. It is a perspective that comes quite readily to the clinician-scientist, and the restoration of that "species" in the era of functional genomics is strongly recommended. Garrod, the initial founder of human "biochemical genetics" belonged to the clinician-scientist community. Archibald Edward Garrod introduced a paradigm, new for its day, in medicine: biochemistry is dynamic and different from the static nature of organic chemistry. It led him to think about metabolic pathways and to recognize that variation in Mendelian heredity could explain an "inborn error of metabolism." At the time, Garrod had no idea about the nature of a gene. Genes are now well understood; genomes are being described for one organism after another (including Homo sapiens) and it is understood that genomes "speak biochemistry (not phenotype)." Accordingly, in the era of genomics, biochemistry and physiology become the bases of functional genomics, and it is possible to appreciate why "nothing in biology makes sense without evolution" (and nothing in medicine will make sense without biology). Mendelian, biochemical and molecular genetics together have revealed what lies behind the 4 canonical inborn errors described by Garrod (albinisn, alkaptonuria, cystinuria and pentosuria). Both older and newer ideas in genetics, new tools for applying them (and renewed respect for the clinician-scientist) will enhance our understanding of the human biological variation that accounts for variant states of health and overt disease. A so-called monogenic phenotype (phenylketonuria) is used to illustrate, in some detail, that all disease phenotypes are, in one way or another, likely to be complex in nature. What can be known and what ought to be done, with knowledge about human genetics, to benefit individuals, families and communities (society), is both opportunity and challenge.

Animals↗
PubMed1991

Deletions of mitochondrial DNA in Kearns-Sayre syndrome and ocular myopathies: genetic, biochemical and morphological studies.

Genetic, biochemical and morphological investigations were conducted on skeletal muscle mitochondria from 6 cases of ocular myopathy: 4 cases with Kearns-Sayre syndrome (KSS) and 2 with chronic progressive external ophthalmoplegia. All of these 6 cases showed mitochondrial DNA (mtDNA) deletions in addition to normal sized DNA in the quadriceps muscle. The deletions ranging from 3 to 8 kbp were also mapped between nucleotides 5500 and 16000 by Southern blot. The deleted genes encoded for some subunits of complexes I, IV, V and 5-10 tRNAS. The boundaries of the deletions have been sequenced in three patients. Five patients had mitochondrial respiratory chain deficiency in complex I as shown by the low oxygen consumption in isolated mitochondria using three NAD(+)-linked substrates. Mitochondria with an abnormal ultrastructure were also observed in 2 cases. A good relationship between the cytochrome c oxidase deficiency and the amount of deleted mtDNA was shown in our present investigations.

Adult↗
PubMed2003

Personnel standards and quality assurance practices of biochemical genetic testing laboratories in the United States.

CONTEXT: It has been suggested that specific regulation of laboratories performing genetic testing may be needed to ensure standards and quality assurance, and to safeguard the rights of patients with regard to confidentiality and providing informed consent. Previously, a comprehensive analysis of current practices of molecular genetic testing laboratories was conducted, the results of which have assisted in the assessment of the need for regulation and its impact on access to testing. However, a study designed to determine clinical laboratory practices with regard to biochemical genetic testing has not been carried out. OBJECTIVE: To collect and analyze data regarding availability of clinical biochemical genetic testing, personnel standards, and laboratory quality assurance practices. DESIGN: A mail survey of biochemical genetic testing laboratory directors and assignment of a quality assurance score based on responses to genetic testing process items. SETTING: Hospital-based, independent, and research-based biochemical genetic testing laboratories in the United States. PARTICIPANTS: Directors of biochemical genetic testing laboratories (n = 133; response rate 68.5%). MAIN OUTCOME MEASURE: Laboratory process quality assurance score based on the standards defined by the American College of Medical Genetics Laboratory Practice Committee. RESULTS: Personnel qualifications varied, although all directors had doctoral degrees. The mean quality assurance score was 77% (range 28%-100%). Higher scores were associated with the following variables: test director having an MD degree versus PhD degree (P = .002), director board certification in biochemical genetics (P = .002), research and hospital laboratory versus independent laboratory setting (P < .001), and participation in a proficiency testing program (P = .03). Twelve percent of participants had a confidentiality policy, and 19% required informed consent before testing. CONCLUSION: The finding that a number of laboratories had quality assurance scores that may reflect suboptimal laboratory practices, particularly with regard to reporting practices, suggests that personnel qualification and laboratory practice standards may be in need of improvement to ensure quality in clinical biochemical genetic testing laboratories, as well as the appropriate clinical use of the test results.

Genetic Diseases, Inborn↗
PubMed1991

Biochemical genetic differences in vulnerability to drug effects: is statistically significant always physiologically important and vice versa?

The goal of biochemical genetic experiments, which are designed to better understand vulnerability to drug effects, is to determine variation in biochemical traits which can account for variation in behavioral and physiological effects of drugs. Biochemical genetic experiments commonly span several distinct scientific disciplines and many different methodologies, both behavioral and biochemical. In most cases, biochemical genetic experiments involve at least three different levels of analysis, including sophisticated mathematical models of genetic inheritance, many behavioral paradigms used to assess various drug-related phenotypes, and a variety of biochemical methodologies used to determine biochemical correlates. Both the multidisciplinary nature of this scientific endeavor and the traditional uses of the scientific methods which are now being applied to pharmacogenetic experiments necessitate careful consideration of many often conflicting theoretical perspectives in the process of interpretation of experimental results. Several scientific considerations are discussed which emphasize the presentation of the results of pharmacogenetic studies within the context of expectations concerning genetic variance as well as traditional uses and assumptions related to methodology.

Animals↗
PubMed1991

Aldehyde dehydrogenase (ALDH) isozymes in the gray short-tailed opossum (Monodelphis domestica): tissue and subcellular distribution and biochemical genetics of ALDH3.

Polyacrylamide gel isoelectric focusing (PAGE-IEF), cellulose acetate electrophoresis, and histochemical techniques were used to examine the tissue and subcellular distribution, genetics and biochemical properties of aldehyde dehydrogenase (ALDH) isozymes in a didelphid marsupial, the gray short-tail opossum (Monodelphis domestica). At least 14 zones of activity were resolved by PAGE-IEF and divided into five isozyme groups and three ALDH classes, based upon comparisons with properties previously reported for human, baboon, rat, and mouse ALDHs. Opossum liver ALDHs were distributed among cytosol (ALDHs 1 and 5) and large granular (mitochondrial) fractions (ALDHs 2 and 5). Similarly, kidney ALDHs were distributed between the cytosol (ALDH5) and the mitochondrial fractions (ALDHs 2, 4, and 5), whereas a major isozyme (ALDH3), found in high activity in cornea, esophagus, ear pinna, tail, and stomach extracts, was localized predominantly in the cytosol fraction. Phenotypic variants of the latter enzyme were shown to be inherited in a normal Mendelian fashion, with two alleles at a single locus (ALDH3) showing codominant expression. The data provided evidence for genetic identity of corneal, ear pinna, tail, and stomach ALDH3 and supported biochemical evidence from other mammalian species that this enzyme has a dimeric subunit structure.

Aldehyde Dehydrogenase↗
PubMed2004

Clinical biochemical genetics in the twenty-first century.

Genetic disorders are recognized to play an increasing role in pediatrics. Close to 10% of diseases among hospitalized children have been ascribed to Mendelian traits inherited as single gene defects, not a surprising figure considering that approximately 1000 inborn errors of metabolism (IEM) have been identified to date, primarily through the detection of endogenous metabolites abnormally accumulated in biological fluids and tissues. The laboratory discipline that covers the biochemical diagnosis of IEM is known as clinical biochemical genetics, and is defined as one concerned with the evaluation and diagnosis of patients and families with inherited metabolic disease, monitoring of treatment, and distinguishing heterozygous carriers from non-carriers by metabolite and enzymic analysis of physiological fluids and tissues. The biochemical genetics laboratory differs from the clinical chemistry laboratory in the extent of interpretation necessary to make its results meaningful to the clinician. While dramatic advances in molecular genetics have greatly changed the landscape of diagnostic options for many genetic disorders, a biochemical approach remains the dominant force for the diagnosis and monitoring of IEM. Owing to the stereotypical clinical presentation of many of these disorders, a major role of the biochemical genetics laboratory is to analyze ever more complex metabolic profiles to reach a preliminary diagnosis, which then needs to be confirmed by enzymic and/or molecular studies in vitro. Accordingly, the role of biochemical genetics in the pediatric practice of the 21st century is to provide a multicomponent screening process that can be divided into four major components: (i) at-risk screening (prenatal diagnosis); (ii) newborn screening (testing of presymptomatic patients); (iii) high-risk screening (testing of symptomatic patients); and (iv) postmortem screening (metabolic autopsy). The focus of our laboratory is to apply state-of-the-art technology such as tandem mass spectrometry to bring as many as possible IEM within the boundaries of newborn screening programs, and to investigate the role played by individual disorders in maternal complications of pregnancy, pediatric acute/fulminant liver failure, and sudden and unexpected death in early life.

Autopsy↗
PubMed1993

Biochemical genetics revisited: the use of mutants to study carbon and nitrogen metabolism in the photosynthetic bacteria.

The biochemical genetics approach is defined as the use of mutants, in comparative studies with the wild-type, to obtain information about biochemical and physiological processes in complex metabolic systems. This approach has been used extensively, for example in studies on the bioenergetics of the photosynthetic bacteria, but has been applied less frequently to studies of intermediary carbon and nitrogen metabolism in phototrophic organisms. Several important processes in photosynthetic bacteria--the regulation of nitrogenase synthesis and activity, the control of intracellular redox balance during photoheterotrophic growth, and chemotaxis--have been shown to involve metabolism. However, current understanding of carbon and nitrogen metabolism in these organisms is insufficient to allow a complete understanding of these phenomena. The purpose of the present review is to give an overview of carbon and nitrogen metabolism in the photosynthetic bacteria, with particular emphasis on work carried out with mutants, and to indicate areas in which the biochemical genetics approach could be applied successfully. In particular, it will be argued that, in the case of Rhodobacter capsulatus and Rb. sphaeroides, two species which are fast-growing, possess a versatile metabolism, and have been extensively studied genetically, it should be possible to obtain a complete, integrated description of carbon and nitrogen metabolism, and to undertake a qualitative and quantitative analysis of the flow of carbon and reducing equivalents during photoheterotrophic growth. This would require a systematic biochemical genetic study employing techniques such as HPLC, NMR, and mass spectrometry, which are briefly discussed. The review is concerned mainly with Rb. capsulatus and Rb. sphaeroides, since most studies with mutants have been carried out with these organisms. However, where possible, a comparison is made with other species of purple non-sulphur bacteria and with purple and green sulphur bacteria, and recent literature relevant to these organisms has been cited.

Amino Acid Sequence↗
PubMed2003

Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress.

CONTEXT: Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered prior to its widespread acceptance as a state-mandated program. OBJECTIVES: To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program. DESIGN: Prospective study involving an inception cohort of newly diagnosed children. SETTING: Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening. PARTICIPANTS: Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases). MAIN OUTCOME MEASURES: Child's health and development and the Parental Stress Index. RESULTS: Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P =.02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P<.001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z = 3.38, P<.001). Children with false-positive results compared with children with normal results were twice as likely to experience hospitalization (21% [n = 20] vs 10% [n = 8], respectively; P =.06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z = 4.25, P<.001) and the Parent-Child Dysfunction subscale (z = 5.30, P<.001). CONCLUSIONS: Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction.

Adult↗
PubMed2004

Brief report: Predictors of parenting stress among parents of children with biochemical genetic disorders.

OBJECTIVE: To examine predictors of parenting stress in parents whose children were diagnosed with a biochemical genetic disorder clinically or through newborn screening. METHODS: Parents of 263 children with biochemical genetic disorders (139 identified by newborn screening, 124 identified clinically) completed interviews focused on child health, medical service use, satisfaction with services, parenting stress, and family functioning. RESULTS: Multiple regression analyses suggested that child adaptive functioning, parental satisfaction with support, and difficulties parents experienced meeting their child's health care needs were associated with scores on the Parenting Stress Index (R2 =.51). CONCLUSIONS: Initiatives to improve child adaptive functioning and parental support as well as practical assistance to help parents meet their child's health needs may reduce parental stress and family disruption in this population.

Adult↗
PubMed1997

[Interlocus associations of various genetic biochemical systems in cattle].

Variation of some genetic biochemical systems (transferrin, ceruloplasmin, amylase-I, and kappa-casein) were studied in five cattle groups of different origin. Data on linkage disequilibrium demonstrated that some syntenic genes did not exhibit interlocus association. Conversely, interlocus association appeared between some loci that were located in different chromosomes. Apparently, the patterns of these associations may be specific for gene pools of individual groups from the same animal species.

Amylases↗
PubMed1982

A nonparametric distance analysis of biochemical genetic data from the Aland Islands, Finland.

Biochemical genetic data from 3272 individuals from the Aland Islands, Finland, are analyzed using a recently developed set of nonparametric genetic distance measures. These measures are more robust than the traditional methods used in previous studies of this population. While there was general agreement in the results of the traditional and nonparametric approaches, some important differences were seen. In these cases, the nonparametric methods gave result more congruent with population history, geographic pripinquity, and migration patterns. Heterozygosity measures were also calculated for the Aland Islands population and compared to values obtained for Jewish populations. The total heterozygosity values were very similar.

Finland↗
PubMed2002

Application of tandem mass spectrometry to biochemical genetics and newborn screening.

Tandem mass spectrometry (MS/MS) has become a key technology in the fields of biochemical genetics and newborn screening. The development of electrospray ionisation (ESI) and associated automation of sample handling and data manipulation have allowed the introduction of expanded newborn screening for disorders which feature accumulation of acylcarnitines and certain amino acids in a number of programs worldwide. In addition, the technique has proven valuable in several areas of biochemical genetics including quantification of carnitine and acylcarnitines, in vitro studies of metabolic pathways (in particular beta-oxidation), and diagnosis of peroxisomal and lysosomal disorders. This review covers some of the basic theory of MS/MS and focuses on the practical application of the technique in these two interrelated areas.

Amino Acids↗
PubMed1990

[Biochemical genetic marker of mouse salivary protein in mouse].

It has been reported by BALAKRSHANN and ASHTON that about 20-30 bands of human salivary protein separated by polyacrylamide gel electrophoresis (PH 8.0) were detected by staining with Coomassie brilliant blue R. Employing the same method, MATSUSHIMA discovered five main regions (I-V) in mouse salivary protein (Msp) separated by poly-acrylamide gel electrophoresis (PH 8.0). He also discovered distinctive features of biochemical genetic markers among each of the five regions. In this experimental study, we investigated biochemical genetic markers of Msp of C3H/HeJ, BALB/c, BALB/k and NOD/shi strains. The following were the results of the present study. 1) The results of C3H/HeJ and BALB/c mice were in accord with those of MATSUSHIMA's. 2) The BALB/k mouse showed the same results as the BALB/c the difference in sex of Msp-1 seemed to have no relation to H-2 complex. 3) With the NOD/she strain, Msp-3 showed the b-type, Msp-2 the a-type, Msp-1 the o-type showed no difference based on sex, that is to say, F-type in both male and female. Amylase-1 showed the b-type.

Animals↗
PubMedDate not supplied

A renaissance of "biochemical genetics"? SNPs, haplotypes, function, and complex diseases.

We have made remarkable progress in understanding the molecular bases of many Mendelian diseases over the past 2-3 decades. The current interest in discovering the molecular basis of complex diseases uses either linkage or candidate gene approaches. The latter often uses case/control (or case/cohort) study designs. We believe it is critically important to have a thorough understanding of SNP (single nucleotide) and haplotype function in such endeavors. Functionally neutral SNPs and haplotypes are probably best suited for linkage studies (far away from the locus of interest). Functionally relevant SNPs and haplotypes seem best suited for candidate gene approaches. The need for functional data may result in a renaissance of biochemical genetics with a new twist in the genomic era. We propose that the functional characterization of SNPs and haplotypes be advanced with great vigor for those genes with defined assayable phenotypes. These systematic investigations will involve classical biochemistry, modern genetics, and genomics and will probably also draw on newer technologies such as microarrays. In short, a renaissance of biochemical genetics will advance our understanding of complex diseases.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

Serological and biochemical genetic markers in congenital cleft lip and cleft palate anomalies.

Serological and biochemical genetic markers in 76 patients with cleft lip with or without cleft palate [CL(P)] and 24 patients with isolated cleft palate (CP) were studied and compared with healthy control subjects. Blood group A phenotype and homozygous plasma haptoglobin (2-2) were found associated with CL(P). The findings suggest that the individuals possessing these markers are more likely to develop congenital CL(P).

ABO Blood-Group System↗