Amino acids in amniotic fluid in the second trimester of gestation.

The concentrations of amino acids in amniotic fluid have been used in the prenatal diagnosis of several inherited metabolic disorders. However, previous studies have usually examined only a small number of control amniotic fluid samples. We have, therefore, measured the amino acids in amniotic fluid samples from 183 normal pregnancies between the 13th and the 23rd wk gestation of women ranging in age from 17 to 43 yr. The concentrations of Ala, Lys, Val, Glu, Pro, Thr, and Gly, in descending order, accounted for about 70% of the amino acids in amniotic fluids. A negative correlation with gestational age (-0.34 to -0.24) was found for Leu, Val, Ile, Phe, Lys, Ala, Asp, Tyr, Glu, and Pro, with Leu showing the greatest rate of change. The concentration of Gln increased slightly (r = 0.18), whereas the other amino acids did not change significantly during this period. Statistically significant positive correlations, at all gestational ages, were observed among Val, Leu, and Ile. These branched-chain amino acids also correlated positively with Phe, Lys, Asp, Thr, Ser, Glu, Pro, Gly, Ala, and Tyr, and the amino acids within this group correlated with each other. Additionally, strong positive correlations were observed between Phe and Tyr and between Gly and Ser. No significant correlations were found between any of the amino acids and maternal age or fetal sex. Significant positive correlations between amino acids may be indicative of common transport or degradative pathways and suggest that maintenance of specific relative concentrations in amniotic fluid may be essential for normal fetal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for an hereditary defect in taurine transport in the ciliary epithelium of an inbred strain of rabbits.

The concentration of taurine in the aqueous humour and serum of 21 rabbits with hereditary buphthalmia (Bu rabbits-genotype bu/bu) was compared with the aqueous and serum taurine levels of eight strain-related normal rabbits (JAX) and nine non-strain-related normal rabbits (MCV). There was a significant difference in the mean aqueous taurine concentration in each of the three groups. The Bu rabbits had only 29% of the MCV rabbits' level while the JAX rabbits were intermediate with 56% of the MCV level. It is suggested that some of the JAX rabbits may be heterozygous and the Bu rabbits homozygous for a semi-dominant allele of a gene that is less efficient in taurine transport in the ciliary epithelium than the normal allele represented by the MCV animals.

Linkage analysis using heterozygote detection in phenylketonuria.

This linkage investigation was undertaken utilizing an improved method for phenylketonuria (PKU) heterozygote detection. This method is based on studies of semi-fasting, noon-time, blood specimens obtained from 85 obligate heterozgotes and 45 controls who were neither pregnant nor on birth control medication. The best separation between heterozygotes and normals was achieved with a discriminant function involving the logarithms of the serum concentrations of phenylalanine, tyrosine and tryptophan. The theoretical overlap area between the distributions of heterozygotes and controls, based on the above function, was between the distributions of heterozygotes and controls, based on the above function, was 3.75%. In 19 obligate heterozygotes and 13 controls who were either pregnant or on birth control medication, the best separation was achieved with a discriminant function involving the logarithms of the serum concentrations of phenylalanine and tyrosine. The theoretical overlap area was 8.23%. These equations identified heterozygotes with sufficient accuracy to permit efficient genetic linkage analysis. We were unable to demonstrate genetic linkage between the PKU locus and 15 common blood, serum, and urinary markers. All but loose linkage (theta greater than 0.3) was excluded for Rh, ABO, Gc, Kidd, and AP. Moderate linkage exclusion (theta less than 0.2) was shown for PGM, Duffy, Hp, MNS, HL--A, and Kell. Close linkage (theta less than 0.1) was excluded for Amy2, 6PGD, P, and ADA. We were unable to find linkage heterogeneity between the Amish and non-Amish populations.

Phenylketonuria heterozygote detection in families with affected children.

Improved approaches to the problem of heterozygote detection for phenylketonuria (PKU) were developed in this study. The discrimination was based on 85 obligate heterozygotes and 45 controls who were neither pregnant nor on birth control medication. The best separation between hetrozygotes and normals was achieved with a linear discriminant function involving the logarithms of the serum concentrations of phenylalanine, tyrosine, and tryptophan. The theoretical overlap area between the distributions of heterozygotes and controls based on the above function, was 3.75%. In the 19 obligate hetrozygotes and 13 controls who were either pregnant or on birth control medication, the best separation was achieved with a linear discriminant function involving the logarithms of the serum concentrations of phenylalanine and tyrosine. The theoretical overlap area was 8.23%. The genetic accuracy of the discriminant function was confirmed by testing the results with parental-child exclusions, segregation analysis, and the frequency of heterozygosity in nonrelated collateral spouses. Finally, there was evidence suggesting that the antihypertensive agent, aldomet, alters serum tyrosine and tryptophan levels.